352 results match your criteria cleaved tau

A delta-secretase-truncated APP fragment activates CEBPB, mediating Alzheimer's disease pathologies.

Brain 2021 Apr 20. Epub 2021 Apr 20.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.

Amyloid-β precursor protein (APP) is sequentially cleaved by secretases and generates amyloid-β, the major components in senile plaques in Alzheimer's disease. APP is upregulated in human Alzheimer's disease brains. However, the molecular mechanism of how APP contributes to Alzheimer's disease pathogenesis remains incompletely understood. Read More

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Pharmacological inhibition of asparaginyl endopeptidase by δ-secretase inhibitor 11 mitigates Alzheimer's disease-related pathologies in a senescence-accelerated mouse model.

Transl Neurodegener 2021 Mar 31;10(1):12. Epub 2021 Mar 31.

Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.

Background: Currently, there is no cure for Alzheimer's disease (AD). Therapeutics that can modify the early stage of AD are urgently needed. Recent studies have shown that the pathogenesis of AD is closely regulated by an endo/lysosomal asparaginyl endopeptidase (AEP). Read More

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Irisin treatment lowers levels of phosphorylated tau in the hippocampus of pre-symptomatic female but not male htau mice.

Neuropathol Appl Neurobiol 2021 Mar 26. Epub 2021 Mar 26.

Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH, 44272, USA.

Aims: Irisin is a hormone cleaved from fibronectin type-III domain-containing protein 5 in response to exercise and may be therapeutic in Alzheimer's disease (AD). Irisin is shown to repair damage caused by midlife cardiometabolic risk factors for AD (i.e. Read More

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Caspase-6-cleaved Tau fails to induce Tau hyperphosphorylation and aggregation, neurodegeneration, glial inflammation, and cognitive deficits.

Cell Death Dis 2021 Mar 1;12(3):227. Epub 2021 Mar 1.

Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.

Active Caspase-6 (Casp6) and Tau cleaved by Casp6 at amino acids 402 (Tau∆D402) and 421 (Tau∆D421) are present in early Alzheimer disease intraneuronal neurofibrillary tangles, which are made primarily of filamentous Tau aggregates. To assess whether Casp6 cleavage of Tau contributes to Tau pathology and Casp6-mediated age-dependent cognitive impairment, we generated transgenic knock-in mouse models that conditionally express full-length human Tau (hTau) 0N4R only (CTO) or together with human Casp6 (hCasp6) (CTC). Region-specific hippocampal and cortical hCasp6 and hTau expression were confirmed with western blot and immunohistochemistry in 2-25-month-old brains. Read More

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μDrop: Multi-analyte portable electrochemical-sensing device for blood-based detection of cleaved tau and neuron filament light in traumatic brain injury patients.

Biosens Bioelectron 2021 Apr 23;178:113033. Epub 2021 Jan 23.

BioMEMS and Bioinspired Microfluidic Laboratory, Department of Mechanical and Manufacturing Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada; Biomedical Engineering Graduate Program, University of Calgary, Calgary, Alberta, T2N 1N4, Canada; Center for Bioengineering Research and Education, Schulich School of Engineering, University of Calgary, Calgary, Alberta, T2N 1N4, Canada. Electronic address:

Over 27 million individuals are affected every year worldwide with central nervous system (CNS) injuries. These injuries include but are not limited to traumatic brain injury (TBI) and spinal cord injury (SCI). CNS injuries remain a significant public health concern which demands reliable tools for rapid, on-sight, on-field, and point-of-care diagnostic (POC) solutions. Read More

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Aberrant role of ALK in tau proteinopathy through autophagosomal dysregulation.

Mol Psychiatry 2021 Jan 15. Epub 2021 Jan 15.

School of Biological Science, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.

Proteinopathy in neurodegenerative diseases is typically characterized by deteriorating activity of specific protein aggregates. In tauopathies, including Alzheimer's disease (AD), tau protein abnormally accumulates and induces dysfunction of the affected neurons. Despite active identification of tau modifications responsible for tau aggregation, a critical modulator inducing tau proteinopathy by affecting its protein degradation flux is not known. Read More

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January 2021

Improves Spatial Learning and Memory by Regulating N-methyl-D-aspartate Receptors and Tau Phosphorylation in Chronic Restraint Stress-Induced Memory Impaired Mice.

Am J Chin Med 2021 26;49(1):69-94. Epub 2020 Dec 26.

Jeonnam Bioindustry Foundation, Jeonnam Institute of Natural Resources, Research (JINR), Jeollanamdo 59338, Republic of Korea.

Thunb. Leaves (VBL) are a component of traditional herbal medicines. However, molecular mechanisms of VBL in stress-related memory impairment are still unclear. Read More

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December 2020

Asparagine Endopeptidase (δ Secretase), an Enzyme Implicated in Alzheimer's Disease Pathology, Is an Inhibitor of Axon Regeneration in Peripheral Nerves.

eNeuro 2021 Jan-Feb;8(1). Epub 2021 Jan 15.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322.

Asparagine endopeptidase (AEP) is a lysosomal protease implicated in the pathology of Alzheimer's disease (AD). It is known to cleave the axonal microtubule associated protein, Tau, and amyloid precursor protein (APP), both of which might impede axon regeneration following peripheral nerve injury (PNI). Active AEP, AEP-cleaved fragments of Tau (Tau N368), and APP (APP N585) were found in injured peripheral nerves. Read More

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January 2021

Loss of DEK Expression Induces Alzheimer's Disease Phenotypes in Differentiated SH-SY5Y Cells.

Front Mol Neurosci 2020 16;13:594319. Epub 2020 Nov 16.

Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.

Alzheimer's disease (AD) is the most common cause of dementia and is characterized by the buildup of β-amyloid plaques and neurofibrillary Tau tangles. This leads to decreased synaptic efficacy, cell death, and, consequently, brain atrophy in patients. Behaviorally, this manifests as memory loss and confusion. Read More

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November 2020

Endosomal Dysfunction Induced by Directly Overactivating Rab5 Recapitulates Prodromal and Neurodegenerative Features of Alzheimer's Disease.

Cell Rep 2020 Nov;33(8):108420

Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA; Department of Psychiatry, New York University Langone Health, New York, NY 10016, USA; Department of Cell Biology, New York University Langone Health, New York, NY 10003, USA; NYU Neuroscience Institute, New York, NY 10003, USA. Electronic address:

Neuronal endosomal dysfunction, the earliest known pathobiology specific to Alzheimer's disease (AD), is mediated by the aberrant activation of Rab5 triggered by APP-β secretase cleaved C-terminal fragment (APP-βCTF). To distinguish pathophysiological consequences specific to overactivated Rab5 itself, we activate Rab5 independently from APP-βCTF in the PA-Rab5 mouse model. We report that Rab5 overactivation alone recapitulates diverse prodromal and degenerative features of AD. Read More

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November 2020

The effects of HIF-1α overexpression on renal injury, immune disorders and mitochondrial apoptotic pathways in renal ischemia/reperfusion rats.

Transl Androl Urol 2020 Oct;9(5):2157-2165

Department of Geriatrics, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, China.

Background: Renal ischemia/reperfusion (RI/R) injury are a common pathogenesis of acute kidney injury, which may cause renal parenchyma damage clinically. Hypoxia-inducible factor-1α (HIF-1α) has protective effects on cells in regulating the metabolism, angiogenesis, erythropoiesis, and anti-apoptosis of RI/R injury. However, the specific mechanisms for HIF-1α on RI/R injury are still unclear. Read More

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October 2020

LncRNA BACE1-AS Promotes Autophagy-Mediated Neuronal Damage Through The miR-214-3p/ATG5 Signalling Axis In Alzheimer's Disease.

Neuroscience 2021 02 13;455:52-64. Epub 2020 Nov 13.

Shaanxi Key Laboratory of Chinese Medicine Encephalopathy, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, PR China. Electronic address:

Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by progressive memory loss and cognitive dysfunction. Long non-coding RNAs (lncRNAs) have been shown to be among the most promising biomarkers and therapeutic targets of AD. Here, we aimed to investigate whether lncRNA BACE1-AS plays a role in the potential mechanisms of AD. Read More

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February 2021

Neuregulin-1 inhibits CoCl-induced upregulation of excitatory amino acid carrier 1 expression and oxidative stress in SH-SY5Y cells and the hippocampus of mice.

Mol Brain 2020 11 13;13(1):153. Epub 2020 Nov 13.

Department of Anatomy and Neuroscience, College of Medicine, Eulji University, 143-5Jung-Gu, Yongdu-Dong, Daejeon, 301-746, Republic of Korea.

Excitatory amino acid carrier 1 (EAAC1) is an important subtype of excitatory amino acid transporters (EAATs) and is the route for neuronal cysteine uptake. CoCl is not only a hypoxia-mimetic reagent but also an oxidative stress inducer. Here, we found that CoCl induced significant EAAC1 overexpression in SH-SY5Y cells and the hippocampus of mice. Read More

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November 2020

Cerebrospinal fluid sTREM2 in Alzheimer's disease: comparisons between clinical presentation and AT classification.

Sci Rep 2020 09 28;10(1):15886. Epub 2020 Sep 28.

Department of Pharmacology, Institute of Clinical Medicine, University of Oslo and Oslo University Hospital, Oslo, Norway.

Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed by microglia. Its cleaved fragments, soluble TREM2 (sTREM2), can be measured in the cerebrospinal fluid (CSF). Previous studies indicate higher CSF sTREM2 in symptomatic AD; however most of these studies have included biomarker positive AD cases and biomarker negative controls. Read More

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September 2020

RPS23RG1 modulates tau phosphorylation and axon outgrowth through regulating p35 proteasomal degradation.

Cell Death Differ 2021 Jan 9;28(1):337-348. Epub 2020 Sep 9.

Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, 361102, Fujian, China.

Tauopathies are a group of neurodegenerative diseases characterized by hyperphosphorylation of the microtubule-binding protein, tau, and typically feature axon impairment and synaptic dysfunction. Cyclin-dependent kinase5 (Cdk5) is a major tau kinase and its activity requires p35 or p25 regulatory subunits. P35 is subjected to rapid proteasomal degradation in its membrane-bound form and is cleaved by calpain under stress to a stable p25 form, leading to aberrant Cdk5 activation and tau hyperphosphorylation. Read More

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January 2021

Truncated Tau Induces Mitochondrial Transport Failure Through the Impairment of TRAK2 Protein and Bioenergetics Decline in Neuronal Cells.

Front Cell Neurosci 2020 30;14:175. Epub 2020 Jul 30.

Laboratory of Neurodegenerative Diseases, Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile.

Mitochondria are highly specialized organelles essential for the synapse, and their impairment contributes to the neurodegeneration in Alzheimer's disease (AD). Previously, we studied the role of caspase-3-cleaved tau in mitochondrial dysfunction in AD. In neurons, the presence of this AD-relevant tau form induced mitochondrial fragmentation with a concomitant reduction in the expression of Opa1, a mitochondrial fission regulator. Read More

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Dimethyl Fumarate Mitigates Tauopathy in Aβ-Induced Neuroblastoma SH-SY5Y Cells.

Neurochem Res 2020 Nov 20;45(11):2641-2652. Epub 2020 Aug 20.

School of Pharmacy, Devi Ahilya Vishwavidyalaya, Takshashila Campus, Khandwa Road, Indore, M.P., 452001, India.

Alzheimer's disease pathogenesis is measured by two key hallmarks viz extracellular senile plaques composed of insoluble amyloid beta (Aβ) and neurofibrillary tangles composed of hyperphosphorylated tau, resulting in microtubule destabilization, synaptic damage and neurodegeneration. Accumulation of Aβ is an introducing pathological incident in Alzheimer's disease; hence, the effect of dimethyl fumarate (DMF) on Aβ-induced alterations in phosphorylated tau, related protein kinases, fibrillogenesis and microtubule assembly in neuroblastoma SH-SY5Y cells was determined. DMF attenuated Aβ-induced neuronal apoptosis by down-regulating protein levels of Bcl-2/Bax, cleaved caspase-3 and caspase-9. Read More

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November 2020

The influence of Aβ-dependent and independent pathways on TDP-43 proteinopathy in Alzheimer's disease: a possible connection to LATE-NC.

Neurobiol Aging 2020 11 2;95:161-167. Epub 2020 Jul 2.

Department of Bionano Technology, Gachon University, Seongnam-si, Republic of Korea. Electronic address:

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that results from the accumulation of plaques by cleaved Aβ peptides as well as neurofibrillary tangles of tau proteins. This accumulation triggers a complex cascade of cytotoxic, neuroinflammatory, and oxidative stresses that lead to neuronal death throughout the progression of the disease. Much of research in AD focused on the 2 pathologic proteins. Read More

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November 2020

Cleavage of human tau at Asp421 inhibits hyperphosphorylated tau induced pathology in a Drosophila model.

Sci Rep 2020 08 10;10(1):13482. Epub 2020 Aug 10.

Institute of Biotechnology, National Tsing Hua University, Hsinchu, 30013, Taiwan.

Hyperphosphorylated and truncated tau variants are enriched in neuropathological aggregates in diseases known as tauopathies. However, whether the interaction of these posttranslational modifications affects tau toxicity as a whole remains unresolved. By expressing human tau with disease-related Ser/Thr residues to simulate hyperphosphorylation, we show that despite severe neurodegeneration in full-length tau, with the truncation at Asp421, the toxicity is ameliorated. Read More

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CSF levels of the BACE1 substrate NRG1 correlate with cognition in Alzheimer's disease.

Alzheimers Res Ther 2020 07 20;12(1):88. Epub 2020 Jul 20.

Inserm U 1144, University de Paris, Paris, France.

Background: The presynaptic protein neuregulin1 (NRG1) is cleaved by beta-site APP cleaving enzyme 1 (BACE1) in a similar way as amyloid precursor protein (APP) NRG1 can activate post-synaptic receptor tyrosine-protein kinase erbB4 (ErbB4) and was linked to schizophrenia. The NRG1/ErbB4 complex is neuroprotective, can trigger synaptogenesis and plasticity, increases the expression of NMDA and GABA receptors, and can induce neuroinflammation. This complex can reduce memory formation. Read More

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Effects of Gastrodin against Lead-Induced Brain Injury in Mice Associated with the Wnt/Nrf2 Pathway.

Nutrients 2020 Jun 17;12(6). Epub 2020 Jun 17.

College of Physical Education, Jiangsu Normal University, No.101, Shanghai Road, Tongshan New Area, Xuzhou 221116, China.

Gastrodin (GAS), the main phenolic glycoside extracted from Blume, exhibited potential neuroprotective properties. Here we examined the protective effects of GAS against lead(Pb)-induced nerve injury in mice, and explores its underlying mechanisms. Our research findings revealed that GAS improved behavioral deficits in Pb-exposed mice. Read More

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Simvastatin Prevents Long-Term Cognitive Deficits in Sepsis Survivor Rats by Reducing Neuroinflammation and Neurodegeneration.

Neurotox Res 2020 Dec 10;38(4):871-886. Epub 2020 Jun 10.

Department of Basic and Oral Biology, School of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café s/n, Ribeirão Preto, SP, CEP 14049-900, Brazil.

Sepsis-associated encephalopathy causes brain dysfunction that can result in cognitive impairments in sepsis survivor patients. In previous work, we showed that simvastatin attenuated oxidative stress in brain structures related to memory in septic rats. However, there is still a need to evaluate the long-term impact of simvastatin administration on brain neurodegenerative processes and cognitive damage in sepsis survivors. Read More

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December 2020

Taurine attenuates liver autophagy and injury of offspring in gestational diabetic mellitus rats.

Life Sci 2020 Sep 2;257:117889. Epub 2020 Jun 2.

Obstetrics Department, Linyi Central Hospital, Shangdong Province 276400, China.

Purpose: Gestational diabetes mellitus (GDM) has many adverse effects on offspring, such as abnormal glycolipid metabolism, obesity, insulin resistance, mental retardation, schizophrenia and so on.

Methods: We established a GDM rat model by injecting 1% streptozotocin associated with a high-fat diet one week before pregnancy, and offspring rats were sacrificed at 8 weeks of age to obtain liver tissue for study. We used hematoxylin-eosin (HE) staining to observe liver morphological changes, Tunel staining for hepatocyte apoptosis, transmission electron microscope for liver ultrastructure, and western blot for protein expression in liver tissue. Read More

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September 2020

The lipid phosphatase Synaptojanin 1 undergoes a significant alteration in expression and solubility and is associated with brain lesions in Alzheimer's disease.

Acta Neuropathol Commun 2020 06 3;8(1):79. Epub 2020 Jun 3.

Laboratory of Histology, Neuroanatomy and Neuropathology, ULB Neuroscience Institute, Université Libre de Bruxelles (ULB), 808, route de Lennik (Bldg G), 1070, Brussels, Belgium.

Synaptojanin 1 (SYNJ1) is a brain-enriched lipid phosphatase critically involved in autophagosomal/endosomal trafficking, synaptic vesicle recycling and metabolism of phosphoinositides. Previous studies suggest that SYNJ1 polymorphisms have significant impact on the age of onset of Alzheimer's disease (AD) and that SYNJ1 is involved in amyloid-induced toxicity. Yet SYNJ1 protein level and cellular localization in post-mortem human AD brain tissues have remained elusive. Read More

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The Role of Mitochondrial Impairment in Alzheimer´s Disease Neurodegeneration: The Tau Connection.

Curr Neuropharmacol 2020 ;18(11):1076-1091

Laboratory of Neurodegenerative Diseases, Facultad de Ciencias de la Salud, Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile

Accumulative evidence has shown that mitochondrial dysfunction plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Mitochondrial impairment actively contributes to the synaptic and cognitive failure that characterizes AD. The presence of soluble pathological forms of tau like hyperphosphorylated at Ser396 and Ser404 and cleaved at Asp421 by caspase 3, negatively impacts mitochondrial bioenergetics, transport, and morphology in neurons. Read More

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January 2020

Experimental evidence for alpha enolase as one potential autoantigen in the pathogenesis of both autoimmune thyroiditis and its related encephalopathy.

Int Immunopharmacol 2020 Aug 19;85:106563. Epub 2020 May 19.

Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, PR China.

Alpha-enolase (ENO1) is a ubiquitous protein. Patients with autoimmune thyroiditis-associated encephalopathy have high serum ENO1Ab titers. We aimed to explore whether ENO1Ab was the pathogenic antibody in the thyroid and brain. Read More

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Physical exercise during exposure to 40-Hz light flicker improves cognitive functions in the 3xTg mouse model of Alzheimer's disease.

Alzheimers Res Ther 2020 05 20;12(1):62. Epub 2020 May 20.

Department of Physiology, College of Medicine, KyungHee University, Seoul, Republic of Korea.

Background: Exercise promotes brain health and improves cognitive functioning in the elderly, while 40-Hz light flickering through the visual cortex reduces amyloid beta (Aβ) by stabilizing gamma oscillation. We examined whether exercise was associated with hippocampus-mediated improvement in cognitive functioning in the 3xTg-Alzheimer's disease (3xTg-AD) murine model following exposure to 40-Hz light flickering and exercise.

Methods: We subjected 12-month-old 3xTg-AD mice to exercise and 40-Hz light flickering for 3 months to investigate spatial learning, memory, long-term memory, Aβ levels, tau levels, mitochondrial functioning including Ca retention and HO emission, apoptosis, and neurogenesis in the hippocampus. Read More

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Experimentally Induced Endometritis Impairs the Developmental Capacity of Bovine Oocytes†.

Biol Reprod 2020 08;103(3):508-520

Department of Large Animal Clinical Sciences, University of Florida, Gainesville FL, USA.

Uterine infection is associated with infertility in women and dairy cows, even after the resolution of infection. However, the mechanisms causing this persistent infertility are unclear. Here, we hypothesized that induced endometritis in non-lactating dairy cows would reduce the developmental competence of oocytes. Read More

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Estrogen Protects Optic Nerve Head Astrocytes Against Oxidative Stress by Preventing Caspase-3 Activation, Tau Dephosphorylation at Ser and the Formation of Tau Protein Aggregates.

Cell Mol Neurobiol 2021 Apr 8;41(3):449-458. Epub 2020 May 8.

Department of Ophthalmology, School of Medicine, Vision Research Center, University of Missouri - Kansas City, 2411 Holmes St., Kansas City, MO, 64108, USA.

Glaucoma is a neurodegenerative disorder that leads to the slow degeneration of retinal ganglion cells, and results in damage to the optic nerve and concomitant vision loss. As in other disorders affecting the viability of central nervous system neurons, neurons affected by glaucoma do not have the ability to regenerate after injury. Recent studies indicate a critical role for optic nerve head astrocytes (ONHAs) in this process of retinal ganglion cell degeneration. Read More

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Cdk5 Inhibitory Peptide Prevents Loss of Neurons and Alleviates Behavioral Changes in p25 Transgenic Mice.

J Alzheimers Dis 2020 ;74(4):1231-1242

Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.

Background: Accumulation of p25 is thought to be a causative risk factor for Alzheimer's disease (AD). As a cleaved product of p35, p25 binds to cyclin-dependent kinase 5 (Cdk5) and leads to the hyperactivity of Cdk5. Then, Cdk5/p25 phosphorylates many pathological substrates related to neurodegenerative diseases. Read More

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January 2020