Publications by authors named "Anmu Xie"

50 Publications

Association between VPS13C rs2414739 polymorphism and Parkinson's disease risk: A meta-analysis.

Neurosci Lett 2021 May 7;754:135879. Epub 2021 Apr 7.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address:

Objective: We aimed to estimate the role of vacuolar protein sorting 13C (VPS13C) gene single nucleotide polymorphism (SNP) rs2414739 variant in the risk of PD by meta-analysis.

Methods: Five eligible case-control studies including 2796 PD cases and 4138 health controls involved in this meta-analysis. The fixed or random effect model was selected based on the heterogeneity of the included studies which detected by I and Q tests. The association between rs2414739 polymorphism and the risk of PD was evaluated using the pooled odds ratios (OR) and 95 % confidence interval (95 %CI). Sensitivity analysis was used to test the stability of the results. Funnel plot and Begg's test were employed to verified publication bias.

Results: The results of our meta-analysis showed a significant correlation between VPS13C rs2424739 gene polymorphism and PD susceptibility in Allele model (A versus vs. G: OR = 1.14, 95 %CI = 1.05-1.23, p = 0.002), dominant model (GG + AG vs. AA: OR = 0.86, 95 %CI = 0.78-0.95, p = 0.004), heterozygote model (AG vs. AA: OR = 0.87, 95 %CI = 0.77-0.99, p = 0.04), homozygote model (GG vs. AA: OR = 0.76, 95 %CI = 0.60-0.96, p = 0.02). Surprisingly, we did not find a significant statistical difference between VPS13C rs2414739 polymorphism and PD risk in Chinese cohort in the regional stratified analysis.

Conclusions: This meta-analysis suggests that VPS13C rs2414739 polymorphism might act as a genetic predisposition factor for PD, whereas does not include Chinese population.
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http://dx.doi.org/10.1016/j.neulet.2021.135879DOI Listing
May 2021

Prevalence and Clinical Features of FOG in Chinese PD Patients, a Multicenter and Cross-Sectional Clinical Study.

Front Neurol 2021 8;12:568841. Epub 2021 Mar 8.

Department of Neurology, School of Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.

Freezing of gait (FOG) is generally considered as an independent symptom of Parkinson's disease (PD) with a complex pathophysiology. There is a wide range of associated clinical features of FOG reported from different studies without consistent conclusion. Thus, a multicenter, cross-sectional study was designed to investigate the prevalence and clinical features of FOG together with its unique contribution quality of life in Chinese PD patients. Eight hundred and thirty eight PD patients were consecutively recruited into this study from 12 hospital centers in six provinces in China. Clinical information, including motor and neuropsychological features as well as pharmacological details, was collected. Of 827 PD patients, 245 (29.63%) reported FOG. The prevalence of FOG was strongly correlated with modified H-Y stages and symptomatic duration ( < 0.01). 84.90% freezers experienced FOG during turning and 88.98% experienced when initiating the first step. Compared with non-freezers, freezers reported longer disease duration (7.73 ± 5.44 vs. 4.69 ± 3.94, < 0.000), higher frequent PIGD phenotype (61.22 vs. 35.91%, < 0.000), higher scores of UPDRS III (32.85 ± 15.47 vs. 22.38 ± 12.89, < 0.000), HAMA (10.99 ± 7.41 vs. 7.59 ± 6.47, < 0.000), HAMD (15.29 ± 10.29 vs. 10.58 ± 8.97, < 0.000) and lower MMSE score (25.12 ± 5.27 vs. 26.63 ± 3.97, < 0.000), and higher daily levodopa dosage (432.65 ± 264.31 vs. 319.19 ± 229.15, < 0.000) with less frequent initial use of dopaminergic agonist (8.57 vs. 14.78%, < 0.05). Using binary logistic regression, the associated factors of FOG might be non-tremor dominant onset (OR = 3.817, < 0.000), the presence of anxiety (OR = 2.048, < 0.000) and imbalance (OR = 4.320, = 0.012). Freezers had poorer quality of life than non-freezers and FOG impacted PDQ-8 independently. Nearly one third of the PD patients experienced FOG. Its frequency increased with PD progression and FOG reduced independently the quality of life. Non-tremor dominant, disease progression, and anxiety were risk factors of FOG.
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http://dx.doi.org/10.3389/fneur.2021.568841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982534PMC
March 2021

Molecular Mechanisms Underlying Reciprocal Interactions Between Sleep Disorders and Parkinson's Disease.

Front Neurosci 2020 10;14:592989. Epub 2021 Feb 10.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Sleep-wake disruptions are among the most prevalent and burdensome non-motor symptoms of Parkinson's disease (PD). Clinical studies have demonstrated that these disturbances can precede the onset of typical motor symptoms by years, indicating that they may play a primary function in the pathogenesis of PD. Animal studies suggest that sleep facilitates the removal of metabolic wastes through the glymphatic system convective flow from the periarterial space to the perivenous space, upregulates antioxidative defenses, and promotes the maintenance of neuronal protein homeostasis. Therefore, disruptions to the sleep-wake cycle have been associated with inefficient metabolic clearance and increased oxidative stress in the central nervous system (CNS). This leads to excessive accumulation of alpha-synuclein and the induction of neuronal loss, both of which have been proposed to be contributing factors to the pathogenesis and progression of PD. Additionally, recent studies have suggested that PD-related pathophysiological alterations during the prodromal phase disrupt sleep and circadian rhythms. Taken together, these findings indicate potential mechanistic interactions between sleep-wake disorders and PD progression as proposed in this review. Further research into the hypothetical mechanisms underlying these interactions would be valuable, as positive findings may provide promising insights into novel therapeutic interventions for PD.
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http://dx.doi.org/10.3389/fnins.2020.592989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902929PMC
February 2021

CUB and Sushi Multiple Domains (CSMD1) Gene Polymorphisms and Susceptibilities to Idiopathic Parkinson's Disease in Northern Chinese Han Population: A Case-Control Study.

Parkinsons Dis 2021 12;2021:6661162. Epub 2021 Feb 12.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.

Evidence has shown that the CUB and Sushi Multiple Domains () gene is an inhibitor of the complement activation pathway and is also involved in central nervous system inflammation. Previous studies have revealed that the gene is related to familial Parkinson's disease. This study aimed to investigate the relationship between gene and susceptibility to Parkinson's disease in population of northern China. A case-control study was performed on 423 Parkinson's disease patients and 465 healthy controls matched for age and sex. DNA from enrolled subjects were extracted from the peripheral blood, and single nucleotide polymorphisms (SNPs) rs12681349 (C>T), rs10503253 (C>A), and rs1983474 (T>G) within CSMD1 gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotype frequency of rs10503253 (CA versus CC : OR = 1.554, 95% CI = 1.169-2.066, =0.002) and rs1983474 (GG versus TT : OR = 0.599, 95% CI = 0.401-0.895, =0.012) was significantly different between PD cases and controls, but not for rs12681349. Comprehensive and subgroup analysis indicated that rs10503252 showed significant statistical differences in the dominant model (AA + CA versus CC : OR = 0.677, 95% CI = 0.517-0.886, =0.004), late-onset cohort (CA versus CC : OR = 1.570, 95% CI = 1.159-2.126, =0.004), and the female cohort (CA versus CC : OR = 0.687, 95% CI = 0.497-0.952, =0.023), compared with the matched control group. The difference of recessive model of rs1983474 (GG versus TT + TG : OR = 1.837, 95% CI = 1.287-2.620, =0.001) was significant in Parkinson's disease. According to the subgroup analysis, results indicated that late-onset cohort (GG versus TT : OR = 0.643, 95% CI = 0.420-0.985, =0.042), male cohort (TG versus TT : OR = 2.160, 95% CI = 1.162-4.016, =0.015), and female group (GG versus TT : OR = 0.418, 95% CI = 0.234-0.746, =0.003) of rs1983474 were significantly associated with Parkinson's disease susceptibility. In both genotype and subgroup analysis, we failed to find any relationship between rs12681349 polymorphism and Parkinson's disease risk. Our results indicate that the rs10503253 and rs1983474 gene polymorphism may be associated with idiopathic Parkinson's disease susceptibility in Chinese population. Nevertheless, these conclusions need to be further verified by more studies.
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http://dx.doi.org/10.1155/2021/6661162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896860PMC
February 2021

MicroRNA expression profiling after recurrent febrile seizures in rat and emerging role of miR-148a-3p/SYNJ1 axis.

Sci Rep 2021 Jan 13;11(1):1262. Epub 2021 Jan 13.

Department of Neurology, Maternal and Child Health Hospital of Weifang Medical University, Weifang, 261011, China.

Febrile seizures (FSs) are common neurological disorders in both infants and children, although the precise underlying mechanism remains to be explored, especially in the expression pattern and function of microRNAs (miRNAs). In this report, we aimed to screen new potential miRNAs and examine the role of miR-148a-3p in hippocampal neurons in FS rats via Synaptojanin-1 (SYNJ1). Thirty rats were randomly divided into the normal and FS model groups, which were investigated by miRNA array. This process identified 31 differentially expressed (20 upregulated and 11 downregulated) miRNAs and potential miRNA target genes. In addition, hippocampal neurons were assigned into five groups for different transfections. Apoptosis was detected by TUNEL and flow cytometry. SYNJ1 was identified as a target gene of miR-148-3p. In vitro experiments revealed that inhibition of miR-148a-3p decreased neuronal cell apoptosis. Moreover, overexpression of miR-148a-3p resulted in activation of PI3K/Akt signaling pathway and the apoptosis of hippocampal neurons. MiR-148a-3p inhibitor could reverse the above events. Taken together, our data demonstrated that the hippocampal miRNA expression profiles of a rat model of FS provide a large database of candidate miRNAs and neuron-related target genes. Furthermore, miR-148a-3p acted as a apoptosis enhcaner via the activation of the SYNJ1/PI3K/Akt signaling pathway, highlighting a potential therapeutic target in the treatment of infants with hyperthermia-induced brain injury.
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http://dx.doi.org/10.1038/s41598-020-79543-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806659PMC
January 2021

Zonisamide for the Treatment of Parkinson Disease: A Current Update.

Front Neurosci 2020 21;14:574652. Epub 2020 Dec 21.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.

Zonisamide has been used as an add-on treatment in order to overcome the deficiencies of the general therapies currently used to resolve the motor complications and non-motor symptoms of Parkinson disease. Various trials have been designed to investigate the mechanism of action and treatment effects of zonisamide in this condition. Most clinical trials of zonisamide in Parkinson disease were from Japan. The vast majority of studies used changes in the Unified Parkinson's Disease Rating Scale (UPDRS) scores and daily "OFF" time as primary endpoints. Based on adequate randomized controlled trials, zonisamide is considered a safe and efficacious add-on treatment in Parkinson disease. The most convincing proof is available for a dosage of 25-50 mg, which was shown to lead to a significant reduction in the UPDRS III score and daily "OFF" time, without increasing disabling dyskinesia. Furthermore, zonisamide may play a beneficial role in improving non-motor symptoms in PD, including impulsive-compulsive disorder, rapid eye movement sleep behavior disorder, and dementia. Among the various mechanisms reported, inhibition of monoamine oxidase-B, blocking of T-type calcium channels, modulation of the levodopa-dopamine metabolism, modulation of receptor expression, and neuroprotection are the most often cited. The mechanisms underlying neuroprotection, including modulation of dopamine turnover, induction of neurotrophic factor expression, inhibition of oxidative stress and apoptosis, inhibition of neuroinflammation, modulation of synaptic transmission, and modulation of gene expression, have been most extensively studied. This review focuses on structure, pharmacokinetics, mechanisms, therapeutic effectiveness, and safety and tolerability of zonisamide in patients with Parkinson disease.
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http://dx.doi.org/10.3389/fnins.2020.574652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779619PMC
December 2020

P2X4R Overexpression Upregulates Interleukin-6 and Exacerbates 6-OHDA-Induced Dopaminergic Degeneration in a Rat Model of PD.

Front Aging Neurosci 2020 4;12:580068. Epub 2020 Nov 4.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.

The pathogenesis of Parkinson's disease (PD) remains elusive. Current thinking suggests that the activation of microglia and the subsequent release of inflammatory factors, including interleukin-6 (IL-6), are involved in the pathogenesis of PD. P2X4 receptor (P2X4R) is a member of the P2X superfamily of ion channels activated by ATP. To study the possible effect of the ATP-P2X4R signal axis on IL-6 in PD, lentivirus carrying the P2X4R-overexpression gene or empty vector was injected into the substantia nigra (SN) of rats, followed by treatment of 6-hydroxydopamine (6-OHDA) or saline 1 week later. The research found the relative expression of P2X4R in the 6-OHDA-induced PD rat models was notably higher than that in the normal. And P2X4R overexpression could upregulate the expression of IL-6, reduce the amount of dopaminergic (DA) neurons in the SN of PD rats, suggesting that P2X4R may mediate the production of IL-6 to damage DA neurons in the SN. Our data revealed the important role of P2X4R in modulating IL-6, which leads to neuroinflammation involved in PD pathogenesis.
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http://dx.doi.org/10.3389/fnagi.2020.580068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671967PMC
November 2020

Identification of Hub Genes of Mesio Temporal Lobe Epilepsy and Prognostic Biomarkers of Brain Low-grade Gliomas Based on Bioinformatics Analysis.

Cell Transplant 2020 Jan-Dec;29:963689720978722

Department of Pediatric, Maternal and Child Health Hospital of Weifang Medical University, Weifang, Shandong, China.

Mesio temporal lobe epilepsy (MTLE) syndrome is the most common form of intractable epilepsies. Meanwhile, seizures are common in patients with cancer as a consequence of brain tumors, including brain low-grade gliomas (LGG). However, the underlying molecular mechanisms of MTLE remain poorly understood. Also, the relationship between MTLE and LGG needs our attention. In this study, we aimed to investigate the hub genes and potential mechanism in MTLE, and the relationship between MTLE and LGG, the gene expression profiles (GSE88992) were downloaded from the Gene Expression Omnibus (GEO) database. Difference analysis for MTLE versus control groups under the three time points was conducted to select the differentially expressed genes (DEGs). Time series clustering analysis was used to select the trend genes. Then a series of bioinformatics analyses including functional enrichment analysis, protein-protein interaction (PPI) network and module analyses, and transcription factor (TF) and miRNA prediction were performed. Also, the overall survival analysis and expression of hub genes in LGG were performed using UALCAN from TCGA database. At 6 h, there were 351 upregulated and 80 downregulated DEGs. At 12 h, there were 499 upregulated and 231 downregulated DEGs. Additionally, 532 upregulated and 402 downregulated DEGs were obtained at 24 h. After time series clustering analysis of the DEGs, we obtained 323 uptrend and 248 downtrend genes. We identified 10 key genes with higher degrees, including C3, TIMP1, PENK, CKAP4, etc. Five PPI modules were identified by MCODE. TF analysis predicted four TFs: JUN, STAT3, NR4A2, and Myc. A total of 26,834 miRNA-mRNA pairs were predicted. Moreover, survival analysis of UALCAN suggested that C3, TIMP1, PENK, GNG2, CKAP4, TNC, JUN, STAT3, NR4A2, and Myc can be potential biomarkers for the prognosis of LGG. In summary, DEGs and hub genes were identified in the present study, which provides novel insight into the development of MTLE.
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http://dx.doi.org/10.1177/0963689720978722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873767PMC
December 2020

Intranasal insulin ameliorates cognitive impairment in a rat model of Parkinson's disease through Akt/GSK3β signaling pathway.

Life Sci 2020 Oct 4;259:118159. Epub 2020 Aug 4.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address:

Aims: Parkinson's disease dementia (PDD) is one of the most common non-motor symptoms of advanced Parkinson's disease (PD). This study aimed to determine whether intranasal insulin has protective effects on cognition in the rat PD model induced by 6-hydroxylase dopamine (6-OHDA) through the insulin signaling pathway.

Materials And Methods: The rats were given intranasal insulin administration for six weeks after unilateral medial forebrain bundle (MFB) injection of 6-OHDA. Then a series of cognitive-behavioral tests, immunofluorescence, and immunoblotting was performed on the rats.

Key Findings: The results demonstrated that the injection of 6-OHDA in the unilateral MFB damaged working memory and long-term habituation of rats in the T-maze rewarded alternation test and hole-board test. Besides, rats with unilateral 6-OHDA injury performed poorly in terms of escape latency and average speed during the hidden platform training phase rather than in the probe trial of the Morris Water Maze (MWM) test. Immunofluorescence results showed that unilateral 6-OHDA injury in MFB led to the massive death of ipsilateral-substantia nigra (SN) tyrosine hydroxylase (TH)-positive neurons. Western blot results further indicated that 6-OHDA-induced necrosis of ipsilateral-SN dopaminergic neurons reduced the levels of p-Akt (Ser473) and p-GSK3β (Ser9) in the ipsilateral-hippocampus.

Significance: These findings provide a solid evidence base for the relationship between PD cognitive impairment and insulin signaling pathways.
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http://dx.doi.org/10.1016/j.lfs.2020.118159DOI Listing
October 2020

Association between epidermal growth factor receptor gene polymorphisms and susceptibility to Parkinson's disease.

Neurosci Lett 2020 09 24;736:135273. Epub 2020 Jul 24.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address:

Objective: The progressive loss of dopaminergic neurons in the mesencephalic substantia nigra is recognized as an important pathological feature of Parkinson's disease (PD). Several research studies have suggested that the EGFR signaling pathway may play a significant role in the survival and functional development of dopaminergic neurons. Therefore, genetic variations in these pathways may be related with PD susceptibility. The aim of our study was to explore the association between selected single nucleotide polymorphisms (SNPs) of the epidermal growth factor receptor (EGFR) gene, including rs730437, rs3752651 and rs11506105, and susceptibility to Parkinson's disease in a Han Chinese population.

Methods: A total of 870 Han Chinese subjects, including 435 PD patients and 435 healthy controls, were enrolled in this case-control study. Peripheral blood was obtained from all subjects for DNA extraction, and selected SNPs (rs730437, rs3752651, rs11506105) of the EGFR gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Differences in the frequencies of genotype and allele gene polymorphisms between patients with PD and healthy controls were analyzed using the Chi-square test. Logistic regression analysis was applied for calculating the odds ratios (ORs) and 95 % confidence intervals (CIs) to evaluate potential associations.

Results: We observed statistically significant differences in rs730437 in the additive models (AC vs. AA: P = 0.047), dominant models (CC + AC vs. AA: P = 0.024) and alleles (C vs. A: P = 0.018). Further subgroup analyses indicated that the C allele of rs730437 showed lower prevalence in the EOPD, compared with matched controls (P = 0.005). The frequency of the GG genotype and G allele for rs11506105 was lower in PD subjects than in healthy controls in the entire study population (P = 0.028, P = 0.034, respectively) and female group (P = 0.024, P = 0.007, respectively). No significant association was found between rs3752651 polymorphism and PD susceptibility in either the whole or subgroup analyses. The analysis of gene haplotypes revealed that the AAT haplotype was related with PD susceptibility.

Conclusion: The rs730437 and rs11506105 polymorphisms, but not the rs3752651 polymorphism, of the EGFR gene may be related with susceptibility to PD in a Han Chinese population. An investigation using a larger sample size is warranted to further analyze potential associations between the EGFR gene and PD.
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http://dx.doi.org/10.1016/j.neulet.2020.135273DOI Listing
September 2020

RAGE Silencing Ameliorates Neuroinflammation by Inhibition of p38-NF-κB Signaling Pathway in Mouse Model of Parkinson's Disease.

Front Neurosci 2020 29;14:353. Epub 2020 Apr 29.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Accumulating evidence suggested that neuroinflammation played a crucial role in dopaminergic neuronal death in Parkinson's disease (PD). The receptor for advanced glycation end products (RAGE), a multi-ligand receptor of the immunoglobulin superfamily, has been proposed as a key molecule in the onset and sustainment of the inflammatory response. Engagement of RAGE contributed to neuroinflammation by upregulating nuclear factor-κB (NF-κB) as well as cytokines. The aim of the present study was to investigate the expression of RAGE in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice and elucidate the RAGE signal pathway involved in the inflammation. Results showed that RAGE protein and pro-inflammatory cytokines cyclooxygenase type 2 (COX-2) were upregulated in MPTP-treated mice. Further experiments showed that RAGE ablation inhibited phosphorylation of IκB and p38 and protected nigral dopaminergic neurons against cell death in the substantia nigra (SN). These results suggested that RAGE participated in the pathogenesis of PD by neuroinflammation and p38MAPK-NFκB signal pathway may be involved in the process. Moreover, interfering with RAGE signaling pathway may be a reasonable therapeutic option in slowing PD development and progression.
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http://dx.doi.org/10.3389/fnins.2020.00353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201072PMC
April 2020

The association between TLR3 rs3775290 polymorphism and sporadic Parkinson's disease in Chinese Han population.

Neurosci Lett 2020 05 23;728:135005. Epub 2020 Apr 23.

Department of Neurology, the Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address:

Accumulating evidences have pointed out that neuroinflammation is involved in Parkinson's disease (PD) pathogenesis. Toll-like receptor 3 (TLR3), as a member of pattern-recognition receptors (PRRs), is known to play a pivotal role in inflammatory responses and immune responses. It was recently suggested that TLR3 was increased in the animal models of PD. The present study aimed to evaluate whether TLR3 gene (rs3775290) polymorphism was associated with PD susceptibility. We genotyped the single-nucleotide polymorphism (SNP) of TLR3 gene (rs3775290) using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) from 380 PD patients and 380 control subjects in Chinese Han population. Our data demonstrated that rs3775290 T allele carriers were associated with a reduced risk of PD between early-onset PD(EOPD)group and its healthy-matched control subgroup (OR = 0.571, 95 %CI = 0.366-0.891, P =  0.013 for TT + TC vs CC). Moreover, there were significant differences in genotype and allele distribution between EOPD group and the late-onset PD (LOPD) group (P = 0.024 and P  = 0.008, respectively). Therefore, our study suggested a possible association between TLR3 (rs3775290) gene polymorphism and PD susceptibility, indicating that T allele of rs3775290 might be a protective factor for sporadic PD in Han Chinese population.
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http://dx.doi.org/10.1016/j.neulet.2020.135005DOI Listing
May 2020

Laquinimod inhibits MMP+ induced NLRP3 inflammasome activation in human neuronal cells.

Immunopharmacol Immunotoxicol 2020 06 5;42(3):264-271. Epub 2020 Apr 5.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.

Nod-like receptor protein 3 (NLRP3) inflammasome plays anessentialrole in neuroinflammation in the Parkinson's disease (PD) progression. Laquinimodis an immunomodulator that is clinically used for the treatment of multiple sclerosis. This study aims to investigate whether laquinimod possessesa protective effect against MPP+-induced NLRP3 activation. In a variety of tests on human SH-SY5Y neuronal cells, 1-methyl-4-phenyl Pyridine (MPP+) was used to mimic the microenvironment of PD. Activation of NLRP3 inflammasome was measured by western blot analysis and enzyme linked immunosorbent assay (ELISA). Laquinimod had a significant protective impact against MPP+-induced neurotoxicity. Our results demonstrate that laquinimod prevented MPP+-induced reduction of cell proliferation, the release of lactate dehydrogenase (LDH), and apoptosis. Importantly, treatment with laquinimod significantly inhibited the activation of the NLRP3 inflammasome by reducing the levels of its components, including NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and cleaved caspase 1 (P10). Consistently, laquinimod prevented MPP+-induced secretions of interleukin 1β (IL-1β) and interleukin-18 (IL-18). Additionally, laquinimod also reduced the expression of other related factors, such as intracellular reactive oxygen species (ROS), NADPH oxidase 4 (NOX-4), thioredoxin-interacting protein (TxNIP). Furthermore, laquinimod prevented the reduction of sirtuin 1 (SIRT1) from MPP+ stimulation. Inhibition of SIRT1 abolished the protective effects of laquinimod against the activation of the NLRP3 inflammasome, suggesting the involvement of SIRT1 in this process. These findings suggest that laquinimod treatment might be a possible therapeutic strategy for neuroinflammation in PD.
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http://dx.doi.org/10.1080/08923973.2020.1746967DOI Listing
June 2020

Association Between Stroke and Parkinson's Disease: a Meta-analysis.

J Mol Neurosci 2020 Aug 17;70(8):1169-1176. Epub 2020 Mar 17.

Department of Neurology, Affiliated Hospital of Qingdao University, No. 16 Jiangsu road, Qingdao, 266003, Shandong Province, People's Republic of China.

Parkinson's disease (PD) and stroke are both associated with aging, but the relationship between these two disorders remains unclear. Recent evidence has shown that they frequently co-occur and are influenced by each another, although some studies have found inconsistent results. We performed this meta-analysis of patients with PD on stroke risk to clarify the relationship between these two disorders on the basis of the studies published from 1975 to July 2019 in the PubMed, EMBASE, and Cochrane Library databases. In total, 13 case-control studies met the inclusion criteria for meta-analysis. The pooled odds ratio (OR) for PD in relation to the stroke risk was 1.72 (95% confidence interval (CI) 1.19-2.49). The OR for the presence of cerebral infarct among PD in the four studies was 1.35 (95% CI 1.04-1.74). Moreover, the OR for the presence of stroke pathology among PD in the four postmortem studies was 1.86 (95% CI 1.17-2.98). In conclusion, our meta-analysis suggests that there is an association between stroke and PD. Sensitivity analysis was used to test the robustness of our results through the sequential removal of each one study at time, in order to investigate if a single study was driving the study results. These results indicate that PD and stroke may have a common pathogenesis and may share preventive treatment measures.
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http://dx.doi.org/10.1007/s12031-020-01524-9DOI Listing
August 2020

Association of IL-16 gene polymorphisms with sporadic Parkinson's disease in a Han Chinese population.

Neurosci Lett 2020 04 28;724:134877. Epub 2020 Feb 28.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China; Neurological Regulation Institute of Qingdao University, China. Electronic address:

This study was performed to investigate the genetic association of single-nucleotide polymorphisms (SNPs) in the interleukin-16 (IL-16) gene with the risk of Parkinson's disease (PD) in a Chinese Han population. Genotyping for the rs11556218 T/G, rs1131445 T/C and rs4072111 C/T polymorphisms of IL-16 was performed using the PCR-RFLP method in 405 patients with PD and 405 healthy matched individuals. Statistically significant difference for rs4072111 could be observed in both additive model (TC vs. CC: OR=0.622, 95 % CI: 0.443-0.873, P = 0.006) and dominant model (TC+TT vs. CC: OR =0.644, 95 % CI: 0.464-0.893, P = 0.008). The frequency of the rs4072111 T allele was significantly lower in the PD patients (OR= 0.692, 95 % CI: 0.515-0.929, P = 0.014) than in the controls. In subgroup analysis, a significant difference in genotype frequency distribution (P =0.004) and allele frequency (P =0.001) was found for rs4072111 between the male PD group and the control group, similar to the findings for the late-onset Parkinson's disease (LOPD) group and the control group (P = 0.044, 0.038, respectively). Conversely, there was no significant difference in the frequencies of rs11556218 and rs1131445 between the PD patients and controls. Moreover, seven common haplotypes were detected, and the CGT and CTC haplotypes were associated with PD susceptibility in our study. Our results indicate that the IL-16 gene rs4072111 polymorphism is significantly associated with PD susceptibility in the Chinese Han population but that the polymorphisms rs11556218 and rs4778889 are not.
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http://dx.doi.org/10.1016/j.neulet.2020.134877DOI Listing
April 2020

Emerging Role of Sirtuin 2 in Parkinson's Disease.

Front Aging Neurosci 2019 10;11:372. Epub 2020 Jan 10.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Parkinson's disease (PD), the main risk factor of which is age, is one of the most common neurodegenerative diseases, thus presenting a substantial burden on the health of affected individuals as well as an economic burden. Sirtuin 2 (SIRT2), a subtype in the family of sirtuins, belongs to class III histone deacetylases (HDACs). It is known that SIRT2 levels increase with aging, and a growing body of evidence has been accumulating, showing that the activity of SIRT2 mediates various processes involved in PD pathogenesis, including aggregation of α-synuclein (α-syn), microtubule function, oxidative stress, inflammation, and autophagy. There have been conflicting reports about the role of SIRT2 in PD, in that some studies indicate its potential to induce the death of dopaminergic (DA) neurons, and that inhibition of SIRT2 may, therefore, have protective effects in PD. Other studies suggest a protective role of SIRT2 in the context of neuronal damage. As current treatments for PD are directed at alleviating symptoms and are very limited, a comprehensive understanding of the enzymology of SIRT2 in PD may be essential for developing novel therapeutic agents for the treatment of this disease. This review article will provide an update on our knowledge of the structure, distribution, and biological characteristics of SIRT2, and highlight its role in the pathogenesis of PD.
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http://dx.doi.org/10.3389/fnagi.2019.00372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965030PMC
January 2020

Association between vitamin D receptor polymorphisms and susceptibility to Parkinson's disease: An updated meta-analysis.

Neurosci Lett 2020 02 21;720:134778. Epub 2020 Jan 21.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, PR China. Electronic address:

The relationships between vitamin D receptor (VDR) gene polymorphisms, particularly ApaI, BsmI, FokI, and TaqI, and Parkinson's disease (PD) has received increasing attention in the research community. However, as the results yielded by this increased research have hitherto conflicted, we performed an updated meta-analysis of reports on the relationships between VDR polymorphisms and PD published before October 2019 that we collected from the PUBMED, EMBASE, EBSCO, China National Knowledge Infrastructure (CNKI), and Wanfang databases. The ten articles that met our screening criteria included 2782 patients and 3194 healthy controls. All the data that we received were analyzed with Stata 12.0 statistical software. The odds ratio (OR) and 95 % confidence intervals (CIs) were used to determine the relationship between VDR gene diversity and PD. While we did not find a significant correlation between the ApaI, BsmI, and TaqI polymorphisms and the risk of PD in any of the considered genetic models, we found a clear association between the FokI polymorphism and susceptibility to PD (C vs. T: OR = 1.246, 95 % CI: 1.101-1.411, P = 0; CC vs. TT: OR = 1.630, 95 % CI: 1.243-2.139, P = 0; CT vs. TT: OR = 1.382, 95 % CI: 1.059-1.804, P = 0.017; CC + CT vs. TT: OR = 1.491, 95 % CI: 1.159-1.919,P = 0.002; CC vs. CT + TT: OR = 1.261, 95 % CI: 1.062-1.496, P = 0.008). Our subgroup analysis performed according to ethnicity revealed that FokI increased the risk of PD in Asian populations (C vs. T: OR = 1.261, 95 % CI: 1.080-1.472, P = 0.003; CC vs. TT: OR = 1.664, 95 % CI: 1.189-2.330, P = 0.003; CT vs.TT: OR = 1.387, 95 % CI: 1.000-1.925, P = 0.05; CC + CT vs. TT: OR = 1.497, 95 % CI: 1.098-2.042, P = 0.011; CC vs. CT + TT: OR = 1.285, 95 % CI: 1.036-1.593, P = 0.022). Overall, the gene polymorphism of FokI only increases the risk of PD among Asian populations. Given the limited sample size of this study, the findings should be carefully explained.
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http://dx.doi.org/10.1016/j.neulet.2020.134778DOI Listing
February 2020

Improvement of Subthalamic Nucleus Deep Brain Stimulation in Sleeping Symptoms in Parkinson's Disease: A Meta-Analysis.

Authors:
Xue Zhang Anmu Xie

Parkinsons Dis 2019 8;2019:6280896. Epub 2019 Oct 8.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.

Introduction: The aim of this meta-analysis was to evaluate the effects of STN DBS on sleep quality and restless leg symptoms in individuals with PD.

Methods: We searched the PubMed, Web of Science, EMBASE, CNKI, and WANFANG databases published between 1990 and 2019. The articles included were those that contained both pre- and postsurgery data acquired using International RLS Study Group criteria and the Pittsburgh sleep quality index (PSQI) questionnaire with patients' follow-up of at least three months. All studies that met the quality requirements were included in a meta-analysis performed using STATA 12.0 software.

Results: Of 73 articles identified, 7 studies comprising 82 patients were qualified for the current meta-analysis. After adjusting for heterogeneity in study effect sizes, the random effects meta-analysis indicated that STN DBS improved sleep quality and restless leg symptoms significantly (SMD = -1.111, 95% CI: -1.918∼-0.304, =0.007). Subgroup analysis showed that different sleep scoring criteria had different effects on the condition of sleeping after surgery.

Conclusions: STN DBS is a powerful method in the management of sleep quality and restless leg symptoms in PD patients, but its long-term effects with larger populations must be thoroughly assessed.
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http://dx.doi.org/10.1155/2019/6280896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800928PMC
October 2019

Association of rs356219 and rs3822086 polymorphisms with the risk of Parkinson's disease: A meta-analysis.

Neurosci Lett 2019 09 17;709:134380. Epub 2019 Jul 17.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, PR China. Electronic address:

Numerous case-control studies have investigated the relationship between rs356219 and rs3822086 polymorphisms and Parkinson's disease (PD) susceptibility. However, these publications have obtained contradictory results. In this study, we conducted a meta-analysis to evaluate the possible association between the two polymorphisms and PD. Literature searches were conducted on PubMed, Web of Science, EMBASE, CNKI and the Wanfang database on studies published until March 2019. Authentic data were calculated utilizing STATA 12.0 statistics software on the data provided in each study. The genetic association between SNCA polymorphisms and the risk of PD was evaluated using the pooled odds ratios (OR) and 95% confidence interval (CI). The results indicate that there is a significant association between rs356219 polymorphism and PD susceptibility for all genetic models (allelic: OR = 1.377, 95% CI: 1.275-1.487, p = 0.000; homozygous: OR = 1.958, 95% CI: 1.666-2.301, p = 0.000; heterozygous: OR = 1.261, 95% CI: 1.158-1.373, p = 0.000; dominant: OR = 1.431, 95% CI: 1.320-1.550, p = 0.000; recessive: OR = 1.632, 95% CI: 1.431-1.861, p = 0.000), which is consistent with the results of the subgroup analyses on Asians and Caucasians. In addition, rs3822086 polymorphism was found to be related to PD in the allelic (OR = 1.249, 95% CI: 1.099-1.419, p = 0.001), homozygous (OR = 1.479, 95% CI: 1.142-1.915, p = 0.003), heterozygous (OR = 1.292, 95% CI: 1.033-1.615, p = 0.025) and dominant (OR = 1.331, 95% CI: 1.030-1.719, p = 0.029) models. Therefore, our results suggest that the presence of SNCA rs356219 and rs3822086 variants may increase the risk of PD.
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http://dx.doi.org/10.1016/j.neulet.2019.134380DOI Listing
September 2019

Prion-Like Mechanisms in Parkinson's Disease.

Front Neurosci 2019 18;13:552. Epub 2019 Jun 18.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.

Formation and aggregation of misfolded proteins in the central nervous system (CNS) is a key hallmark of several age-related neurodegenerative diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). These diseases share key biophysical and biochemical characteristics with prion diseases. It is believed that PD is characterized by abnormal protein aggregation, mainly that of α-synuclein (α-syn). Of particular importance, there is growing evidence indicating that abnormal α-syn can spread to neighboring brain regions and cause aggregation of endogenous α-syn in these regions as seeds, in a "prion-like" manner. Abundant studies and have shown that α-syn goes through a templated conformational change, propagates from the original region to neighboring regions, and eventually cause neuron degeneration in the substantia nigra and striatum. The objective of this review is to summarize the mechanisms involved in the aggregation of abnormal intracellular α-syn and its subsequent cell-to-cell transmission. According to these findings, we look forward to effective therapeutic perspectives that can block the progression of neurodegenerative diseases.
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http://dx.doi.org/10.3389/fnins.2019.00552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591488PMC
June 2019

Determinants of diagnostic latency in Chinese people with Parkinson's disease.

BMC Neurol 2019 Jun 11;19(1):120. Epub 2019 Jun 11.

Department of Neurology, Xinhua Hospital, Affiliated to Shanghai JiaoTong University, School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.

Background: Clinical diagnosis of Parkinson's disease (PD) has always lagged behind clinical symptoms. The diagnostic latency might be influenced by many factors. The diagnostic latency of Chinese people with PD has been unknown. Here we designed this cross-sectional study with the purpose to identify the diagnostic latency and its determinants in Chinese people with PD.

Methods: One hundred and thirty-one newly diagnosed people with PD were recruited into this study. Demographic and clinical characteristics as well as a detailed clinical history were collected. Motor and non-motor symptoms (NMSs) severity were assessed with appropriate assessment scales. Medical professional types in the first medical consultations were also recorded. According to the initially presenting motor phenotypes, patients would be divided into the groups of rest tremor, limb rigidity, movement slowness and walking problems. The investigated variables would be compared among the four groups.

Results: The PD diagnostic latency in China was around 15 months. It closely correlated to the severity of motor symptoms, anxiety and depression as well as the number of NMSs. The diagnostic latency significantly varied among the groups of different motor phenotypes of onset. Finally, initially presenting with limb rigidity, having more NMSs, motor symptoms at a more serious degree and the initial medical consultations with physicians or specialists of non-neurology were considered as determinants of a longer diagnostic latency of PD.

Conclusions: Patients presenting with minor motor symptoms and disturbing NMSs as well as physicians' unfamiliarity with PD symptomology were determinants of the diagnostic delay of PD. Health education in community and improvement of the referral system might be proper strategies to shorten the diagnostic latency of PD.
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http://dx.doi.org/10.1186/s12883-019-1323-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558921PMC
June 2019

Apathy following Bilateral Deep Brain Stimulation of Subthalamic Nucleus in Parkinson's Disease: A Meta-Analysis.

Parkinsons Dis 2018 21;2018:9756468. Epub 2018 May 21.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Bilateral deep brain stimulation of subthalamic nucleus (STN-DBS) has proven effective in improving motor symptoms in Parkinson's disease (PD) patients. However, psychiatric changes after surgery are controversial. In this study, we specifically analyzed apathy following bilateral STN-DBS in PD patients using a meta-analysis. Relevant articles utilized for this study were obtained through literature search on PubMed, ScienceDirect, and Embase databases. The articles included were those contained both pre- and postsurgery apathy data acquired using the Starkstein Apathy Scale or Apathy Evaluation Scale with patient follow-up of at least three months. A total of 9 out of 86 articles were included in our study through this strict screening process. Standardized mean difference (SMD), that is, Cohen's d, with a 95% confidence interval (CI) was calculated to show the change. We found a significant difference between the presurgery stage and the postsurgery stage scores (SMD = 0.35, 95% CI: 0.17∼0.52, < 0.001). STN-DBS seems to relatively worsen the condition of apathy, which may result from both the surgery target (subthalamic nucleus) and the reduction of dopaminergic medication. Further studies should focus on the exact mechanisms of possible postoperative apathy in the future.
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http://dx.doi.org/10.1155/2018/9756468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987292PMC
May 2018

The Role of Insulin/IGF-1/PI3K/Akt/GSK3β Signaling in Parkinson's Disease Dementia.

Front Neurosci 2018 20;12:73. Epub 2018 Feb 20.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China.

Dementia, a condition that frequently afflicts patients in advanced stages of Parkinson's disease (PD), results in decreased quality of life and survival time. Nevertheless, the pathological mechanisms underlying Parkinson's disease dementia (PDD) are not completely understood. The symptoms characteristic of PDD may be the result of functional and structural deficiencies. The present study implicates the accumulation of Lewy bodies in the cortex and limbic system as a potent trigger in the development of PDD. In addition, significant Alzheimer-type pathologies, including amyloid-β (Aβ) plaques and NFTs, are observed in almost half of PDD patients. Interestingly, links between PDD pathogenesis and the mechanisms underlying the development of insulin resistance have begun to emerge. Furthermore, previous studies have demonstrated that insulin treatment reduces amyloid plaques in Alzheimer's disease (AD), and normalizes the production and functionality of dopamine and ameliorates motor impairments in 6-OHDA-induced rat PD models. GSK3β, a downstream substrate of PI3K/Akt signaling following induction by insulin and IGF-1, exerts an influence on AD and PD physiopathology. The genetic overexpression of GSK3β in cortex and hippocampus results in signs of neurodegeneration and spatial learning deficits in models (Lucas et al., 2001), whereas its inhibition results in improvements in cognitive impairment in these rodents, including AD and PD. Accordingly, insulin- or IGF-1-activated PI3K/Akt/GSK3β signaling may be involved in PDD pathogenesis, at least in the pathology of PD-type + AD-type.
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http://dx.doi.org/10.3389/fnins.2018.00073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826217PMC
February 2018

RAGE and its emerging role in the pathogenesis of Parkinson's disease.

Neurosci Lett 2018 04 21;672:65-69. Epub 2018 Mar 21.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address:

Receptor for advanced glycation end products (RAGE) is a multiligand receptor belonging to the immunoglobulin superfamily and plays crucial roles in the development of many human diseases such as neurodegenerative diseases, diabetes, cardiovascular diseases, osteoarthritis and cancer. RAGE involves in a number of cell processes such as neuroinflammation, apoptosis, proliferation and autophagy. In CNS, RAGE was primarily expressed in neurons, microglia and vascular endothelial cells. Interacting with ligands, RAGE induces a series of signal transduction cascades and leads to the activation of transcription factor NF-κB as well as increased expression of cytokines like TNF-α, IL-1. Moreover, binding to RAGE can also stimulate the generation of reactive oxygen species (ROS), which is implicated in neuron death. It was reported that RAGE were highly expressed in PD patients when compared to age-matched controls. And RAGE ablation protected nigral dopaminergic neurons against cell death in MPTP treated mice. Here we review this article to elucidate the role of RAGE in PD pathogenesis and highlight the anti-RAGE strategies in the treatment of PD.
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http://dx.doi.org/10.1016/j.neulet.2018.02.049DOI Listing
April 2018

Association between rs823128 polymorphism and the risk of Parkinson's disease: A meta-analysis.

Neurosci Lett 2018 02 27;665:110-116. Epub 2017 Nov 27.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, PR China. Electronic address:

Numerous published case-control studies have investigated a role of PARK16 gene in susceptibility to Parkinson's disease (PD), but the results remain conflicting and under-powered. Herein, we performed this meta-analysis to evaluate the possible association between the polymorphism of the PARK16 rs8231128 (A/G) and PD.A comprehensive search of six databases was conducted to identify all case-control studies involving PARK16rs823128variants and PD risk up to August 2017. The strict inclusion and exclusion criteria were applied. A total of 9 studies including 15 case-control studies with 7277 PD cases and 6188 controls were included in the meta-analysis. And STATA 12.0 statistics software was used to calculate available data from each study. The crude odds ratios (OR) and 95% confidence interval (CI) were calculated to assess the genetic association between PARK16 rs823128 polymorphism and the risk of PD. In the combined analysis, results showed a significant association between rs823128 and PD in allelic model(G vs. A: OR=0.886, 95% CI=0.811-0.969, P=0.008), dominant model (GG+ AG vs. AA: OR=0.886, 95% CI=0.804-0.976, P=0.014), and heterozygote model (AG vs. AA: OR=0.897, 95% CI=0.812-0.991, P=0.032). Further, ethnicity based analysis showed a significant association in Asian and Chilean population, but not in Caucasian samples. Within its limitations, this meta-analysis demonstrated that the rs823128 variants(G allele, GA and GG genotype)in PARK16 might be a potential protective factor for PD. However, these associations vary in different ethnicities.
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http://dx.doi.org/10.1016/j.neulet.2017.11.057DOI Listing
February 2018

Relationship between mitochondrial DNA A10398G polymorphism and Parkinson's disease: a meta-analysis.

Oncotarget 2017 Sep 15;8(44):78023-78030. Epub 2017 Sep 15.

Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Many studies have researched the mitochondrial DNA (mtDNA) A10398G in Parkinson's disease (PD) to determine the association between mtDNA A10398G and PD, but the results of their research were not consistent. Therefore, we performed a meta-analysis to demonstrate the connection between mtDNA A10398G and the susceptibility of PD. We searched PubMed, Web of Science, Springer Link, EMBASE and EBSCO databases up to identify relevant studies. Through strict inclusion and exclusion criteria, at last, 9 studies (total 3381 cases and 2810 controls) were included in our meta-analysis. We used the STATA 12.0 statistics software to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the genetic association between mtDNA A10398G and the risk of PD. We performed subgroup analysis to clarify the possible roles of the mtDNA A10398G polymorphism in the aetiology of PD in different ethnicities. Our meta-analysis indicates that although there was no significant association between mtDNA A10398G and PD in the Asian population (G vs. A: OR = 1.090, 95% CI = 0.939-1.284, = 0.242), in the Caucasian population the G allele of mtDNA A10398G mutations may be a potential protective factor of PD (G vs. A: OR = 0.699, 95% CI = 0.546-0.895, = 0.005). Further well-designed studies with larger samples are needed to validate these results.
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http://dx.doi.org/10.18632/oncotarget.20920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652833PMC
September 2017

MTHFR C677T and A1298C polymorphisms may contribute to the risk of Parkinson's disease: A meta-analysis of 19 studies.

Neurosci Lett 2018 Jan 31;662:339-345. Epub 2017 Oct 31.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China, China. Electronic address:

The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been reported to be a candidate gene for susceptibility to Parkinson's disease (PD), but results of different studies are conflicting. Here, we conducted a meta-analysis of published case-control studies to evaluate the association between MTHFR C677T and A1298C gene polymorphisms with the risk of PD. Electronic search through PubMed, EmBase, ScienceDirect and Cochrane Library was conducted to identify all relevant studies. A total of 19 studies with 2746 cases and 8967 controls were included. No significant association between MTHFR C677T polymorphism and PD risk was found in the overall population in all five genetic models. In the subgroup analysis stratified by ethnicity, a significant association between MTHFR C677T and PD risk was observed in the dominant model in Caucasians (OR=1.175, 95%CI: 1.008-1.369, P=0.040), but not in Asians. Significant association was found between MTHFR A1298C polymorphism and PD risk in the overall population in the dominant (OR=1.168, 95%CI: 1.008-1.353, P=0.039) and heterozygous model (OR=1.172, 95%CI: 1.004-1.367, P=0.044). But in the subgroup analysis, no association was found between MTHFR A1298C and PD neither in Caucasians nor in Asians. Our meta-analysis suggests that MTHFR C677T polymorphism may be associated with increased PD risk in Caucasians and MTHFR A1298C polymorphism may also increase susceptibility to PD.
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http://dx.doi.org/10.1016/j.neulet.2017.10.060DOI Listing
January 2018

Association between SNCA rs2736990 polymorphism and Parkinson's disease: a meta-analysis.

Neurosci Lett 2017 Sep 24;658:102-107. Epub 2017 Aug 24.

Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address:

Emerging evidence suggests that the SNP rs2736990 of SNCA is a susceptibility factor for idiopathic Parkinson's disease (PD) in different populations, but the studies which examined the association have provided inconsistent results. Therefore, we performed a meta-analysis of some case-control studies to obtain a more exact estimation of there associations. All the relevant studies were extracted from PubMed, Embase, EBSCO, Chineses national knowledge infrastructure, Google Scholar and Wanfang databases (up to February 2017). A total of six studies with 2525 PD cases and 2165 controls were eventually enrolled in the present meta-analysis based on the strict inclusion and exclusion criteria. The pooled analysis showed that there is a significant association between rs2736990 polymorphism and PD susceptibility in all genetic models (T vs. C: OR=0.772, 95%CI: 0.709-0.840, P=0.001; TT vs. CC: OR=0.586, 95%CI: 0.490-0.701, P=0.001; TC vs. CC: OR=0.814, 95%CI: 0.716-0.925, P=0.002; TT+TC vs. CC: OR=0.752, 95%CI: 0.666-0.848, P=0.001; TT vs. TC+CC: OR=0.658, 95%CI: 0.561-0.772, P=0.001). Our meta-analysis provides evidence that the T allele, TT and TC genotype of rs2736990(C/T) polymorphism may decrease the risk of PD.
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http://dx.doi.org/10.1016/j.neulet.2017.08.051DOI Listing
September 2017

Single nucleotide polymorphisms in the toll-like receptor 2 (TLR2) gene are associated with sporadic Parkinson's disease in the North-eastern Han Chinese population.

Neurosci Lett 2017 Aug 17;656:72-76. Epub 2017 Jul 17.

Department of Neurology, The Affiliated Hospital of Qingdao University, China. Electronic address:

Growing evidences suggested that inflammatory process played a critical role in the pathogenesis of Parkinson's disease (PD). Given that TLR2 has been implicated in the perpetuation of inflammatory responses in the central nervous system (CNS), we investigated the association between two genetic variants (rs3804099 and rs3804100) of TLR2 and sporadic PD in Han Chinese population. 395 Han Chinese sporadic PD patients and 413 healthy age and gender-matched controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The sporadic PD patients showed a higher T allele frequency than the healthy-matched control (p=0.019). Furthermore rs3804099 dominate model TT versus (vs.) TC+CC increase the risk of sporadic PD (OR=1.376, 95%CI=1.043-1.814, p=024). From the subgroup analysis, the variant allele T of rs3804099 was higher in sporadic PD cases (73.1%) than in controls (67.4%) in the late-onset cohort. Meanwhile rs3804099 revealed significant association in dominant model: Subjects with TT genotypes vs. those with TC+CC genotype showed evident significant in late-onset cohort (LOPD OR=1.417, 95%CI=1.051-1.911, p=022). In contrast, allele frequencies at rs3804100 were similar between patients and controls. Taken together, this study reveals that polymorphism of TLR2 locus is associated with risk of sporadic PD in the North-eastern part of Han Chinese population. Further studies are required to evaluate the association.
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http://dx.doi.org/10.1016/j.neulet.2017.07.014DOI Listing
August 2017

Assessments of plasma ghrelin levels in the early stages of parkinson's disease.

Mov Disord 2017 Oct 6;32(10):1487-1491. Epub 2017 Jul 6.

Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, China.

Background: Gastrointestinal symptoms are early events in Parkinson's disease (PD). The gastrointestinal hormone ghrelin was neuroprotective in the nigrostriatal dopamine system. The objective of this study was to assess ghrelin levels in the early stages of PD.

Methods: Plasma was collected in the fasting state in 291 PD patients in stages 1-3 and 303 age- and sex-matched healthy controls. Additional samples were taken in the glucose response test to assess nutrition-related ghrelin levels in 20 PD patients and 20 healthy controls. The enzyme-linked immunosorbent assay was used to measure total and active plasma ghrelin levels.

Results: We reported that total and active plasma ghrelin levels were decreased in PD, although there was no difference across progressive PD stages. Postprandial ghrelin suppression and preprandial peak responses were both attenuated in PD.

Conclusions: Plasma ghrelin levels were decreased in PD; however, this event might be irrelevant to PD progression. Ghrelin responses to meals were also impaired in PD. © 2017 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27095DOI Listing
October 2017