Publications by authors named "Jerzy Leszek"

62 Publications

Nuclear Envelope and Nuclear Pore Complexes in Neurodegenerative Diseases-New Perspectives for Therapeutic Interventions.

Mol Neurobiol 2021 Mar 17;58(3):983-995. Epub 2020 Oct 17.

Department of Psychiatry, Wroclaw Medical University, Wybrzeże L. Pasteura 10, 50-367, Wroclaw, Poland.

Transport of proteins, transcription factors, and other signaling molecules between the nucleus and cytoplasm is necessary for signal transduction. The study of these transport phenomena is particularly challenging in neurons because of their highly polarized structure. The bidirectional exchange of molecular cargoes across the nuclear envelope (NE) occurs through nuclear pore complexes (NPCs), which are aqueous channels embedded in the nuclear envelope. The NE and NPCs regulate nuclear transport but are also emerging as relevant regulators of chromatin organization and gene expression. The alterations in nuclear transport are regularly identified in affected neurons associated with human neurodegenerative diseases. This review presents insights into the roles played by nuclear transport defects in neurodegenerative disease, focusing primarily on NE proteins and NPCs. The subcellular mislocalization of proteins might be a very desirable means of therapeutic intervention in neurodegenerative disorders.
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http://dx.doi.org/10.1007/s12035-020-02168-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878205PMC
March 2021

The Links between Cardiovascular Diseases and Alzheimer's Disease.

Curr Neuropharmacol 2021 ;19(2):152-169

I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 8/2 Trubetskaya Str., Moscow, 119991, Russian Federation.

The root cause of non-inherited Alzheimer's disease (AD) remains unknown despite hundreds of research studies performed to attempt to solve this problem. Since proper prophylaxis remains the best strategy, many scientists have studied the risk factors that may affect AD development. There is robust evidence supporting the hypothesis that cardiovascular diseases (CVD) may contribute to AD progression, as the diseases often coexist. Therefore, a lack of well-defined diagnostic criteria makes studying the relationship between AD and CVD complicated. Additionally, inflammation accompanies the pathogenesis of AD and CVD, and is not only a consequence but also implicated as a significant contributor to the course of the diseases. Of note, АроЕε4 is found to be one of the major risk factors affecting both the cardiovascular and nervous systems. According to genome wide association and epidemiological studies, numerous common risk factors have been associated with the development of AD-related pathology. Furthermore, the risk of developing AD and CVDs appears to be increased by a wide range of conditions and lifestyle factors: hypertension, dyslipidemia, hypercholesterolemia, hyperhomocysteinemia, gut/oral microbiota, physical activity, and diet. This review summarizes the literature and provides possible mechanistic links between CVDs and AD.
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http://dx.doi.org/10.2174/1570159X18666200729093724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033981PMC
January 2021

Sleep Disturbances and Cognitive Impairment in the Course of Type 2 Diabetes-A Possible Link.

Curr Neuropharmacol 2021 ;19(1):78-91

I. M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 8/2 Trubetskaya Str., Moscow, 119991, Russian Federation.

There is an increasing number of patients worldwide with sleep disturbances and diabetes. Various sleep disorders, including long or short sleep duration and poor sleep quality of numerous causes, may increase the risk of diabetes. Some symptoms of diabetes, such as painful peripheral neuropathy and nocturia, or associated other sleep disorders, such as sleep breathing disorders or sleep movement disorders, may influence sleep quality and quantity. Both sleep disorders and diabetes may lead to cognitive impairment. The risk of development of cognitive impairment in diabetic patients may be related to vascular and non-vascular and other factors, such as hypoglycemia, hyperglycemia, central insulin resistance, amyloid and tau deposits and other causes. Numerous sleep disorders, e.g., sleep apnea, restless legs syndrome, insomnia, and poor sleep quality are most likely are also associated with cognitive impairment. Adequate functioning of the system of clearance of the brain from toxic substances, such as amyloid β, i.e. glymphatic system, is related to undisturbed sleep and prevents cognitive impairment. In the case of coexistence, sleep disturbances and diabetes either independently lead to and/or mutually aggravate cognitive impairment.
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http://dx.doi.org/10.2174/1570159X18666200309101750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903492PMC
January 2021

Münchausen Syndrome as an Unusual Cause of Pseudo-resistant Hypertension: A Case Report.

Open Med (Wars) 2019 7;14:792-796. Epub 2019 Nov 7.

Cardiology Department, Wroclaw Medical University, 50-367 Wroclaw, Poland.

Münchausen syndrome can be characterized by simulated illness, pathological lying and wandering from place to place (the patient typically presents to numerous hospitals). Individuals with elevated blood pressure due to non-adherence to medication have the so-called pseudo-resistant hypertension. A 45-year-old woman was admitted to hospital on an emergency basis because of a hypertensive crisis. Despite combination antihypertensive treatment, normalization of blood pressure was not achieved and a device to produce a therapeutic arteriovenous fi stula was implanted. Aft er the procedure, a signifi cant increase in pulmonary artery pressure was observed and closure of the fistula was performed by implantation of the stent graft . The suspicion was raised that the patient had not been taking her prescribed medications. Therefore, blood samples were taken and the serum was analyzed for presence of the prescribed drugs (atorvastatin, bisoprolol, chlorthalidone, clonidine, doxazosin, furosemide, nitrendipine, oxazepam and valsartan). The results confirmed suspected failure of the patient to take the prescribed medications. Münchausen syndrome is usually first suspected when inexplicable laboratory test results are noted. To our knowledge, this is the first reported case of Münchausen syndrome with pseudo-resistant hypertension leading to the implantation of a device to produce a therapeutic arteriovenous fi stula.
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http://dx.doi.org/10.1515/med-2019-0094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843548PMC
November 2019

Hampering Herpesviruses HHV-1 and HHV-2 Infection by Extract of (EGb) and Its Phytochemical Constituents.

Front Microbiol 2019 15;10:2367. Epub 2019 Oct 15.

Department of Psychiatry, Wrocław Medical University, Wrocław, Poland.

Despite the availability of several anti-herpesviral agents, it should be emphasized that the need for new inhibitors is highly encouraged due to the increasing resistant viral strains as well as complications linked with periods of recurring viral replication and reactivation of latent herpes infection. Extract of (EGb) is a common phytotherapeutics around the world with health benefits. Limited studies, however, have addressed the potential antiviral activities of EGb, including herpesviruses such as (HHV-1) and (HHV-2). We evaluated the antiviral activity of EGb and its phytochemical constituents: flavonoids and terpenes against HHV-1 and HHV-2. Pretreatment of the herpesviruses with EGb prior to infection of cells produced a remarkable anti-HHV-1 and anti-HHV-2 activity. The extract affected the viruses before adsorption to cell surface at non-cytotoxic concentrations. In this work, through a comprehensive anti-HHV-1 and anti-HHV-2 activity study, it was revealed that flavonoids, especially isorhamnetin, are responsible for the antiviral activity of EGb. Such activity was absent in quercetin and kaempferol. However, EGb showed the most potent antiviral potency compared to isorhamnetin. EGb could augment current therapies for herpes labialis and genital herpes. Moreover, the potential use of EGb in multidrug therapy with synthetic anti-herpes compounds might be considered.
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http://dx.doi.org/10.3389/fmicb.2019.02367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803450PMC
October 2019

Diet and Alzheimer's dementia - Nutritional approach to modulate inflammation.

Pharmacol Biochem Behav 2019 09 26;184:172743. Epub 2019 Jul 26.

Department and Clinic of Psychiatry, Wroclaw Medical University, Wroclaw, Poland. Electronic address:

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease causing dementia in the elderly population. Due to the fact that there is still no cure for Alzheimer's dementia and available treatment strategies bring only symptomatic benefits, there is a pressing demand for other effective strategies such as diet. Since the inflammation hypothesis gained considerable significance in the AD pathogenesis, elucidating the modulatory role of dietary factors on inflammation may help to prevent, delay the onset and slow the progression of AD. Current evidence clearly shows that synergistic action of combined supplementation and complex dietary patterns provides stronger benefits than any single component considered separately. Recent studies reveal the growing importance of novel factors such as dietary advanced glycation end products (d-AGE), gut microbiota, butyrate and vitamin D on inflammatory processes in AD.

Conclusion: This paper summarizes the available evidence of pro- and anti-inflammatory activity of some dietary components including fatty acids, vitamins, flavonoids, polyphenols, probiotics and d-AGE, and their potential for AD prevention and treatment.
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http://dx.doi.org/10.1016/j.pbb.2019.172743DOI Listing
September 2019

WITHDRAWN: Association Between Alzheimer’s Disease and Cancer - A Short Overview

Curr Med Chem 2019 07 16. Epub 2019 Jul 16.

Department and Clinic of Psychiatry, Wroclaw Medical University, Wroclaw. Poland.

The following article has been withdrawn at the request of the authors and editor of the journal Current Medicinal Chemistry: Title: Association between Alzheimer's Disease and Cancer - A Short Overview. Authors: Katarzyna Szczechowiak, Anna Brzecka, Naomi Hachiya, Joanna Wyka and Jerzy Leszek* Bentham Science apologizes to the readers of the journal for any inconvenience this may cause. Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.
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http://dx.doi.org/10.2174/0929867326666190716130150DOI Listing
July 2019

New therapeutic targeting of Alzheimer's disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response - preliminary study.

J Neuroinflammation 2019 Jul 5;16(1):137. Epub 2019 Jul 5.

Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland.

Background: The lack of effective treatment for Alzheimer's disease (AD) stems mainly from the incomplete understanding of AD causes. Neuroinflammation has emerged as an important component of AD pathology, and a vast number of experimental and clinical data indicated a crucial role for the activation of the innate immune system in disease promotion and symptom progression.

Methods: Clinical examinations of AD patients in a different stage of disease severity in correlation with the measurement of two innate immune reactions, i.e., peripheral blood leukocyte (PBLs) resistance to viral infection (vesicular stomatitis virus, VSV) ex vivo, and cytokines: TNF-α, IFN-γ, IL-1β, and IL-10, production with enzyme-linked immunosorbent assay (ELISA), have been investigated during this preliminary study before and after 4 weeks of oral treatment with dietary supplement proline-rich polypeptide complex (PRP) (120 μg of PRP/day). The potential effect of PRP on the distribution of PBLs' subpopulations has been specified.

Results: We have found a deficiency in innate immune response in AD patients. It was demonstrated for the first time that the degree of PBLs resistance to VSV infection was closely related to the stage of clinical severity of AD. Our study showed significant differences in cytokine production which pointed that in AD patients innate immune mechanisms are impaired. Administration of PRP to our patients increased innate immune response of PBLs and declined pro- and anti-inflammatory cytokine production, thus subduing the excessively developed inflammatory response, especially among patients with high severity of AD. PRP did not exhibit a pro-proliferative activity. It was showed, however, significant influence of PRP on the distribution of PBLs' subpopulations.

Conclusion: The findings mentioned above might be crucial in the context of potential application of immunomodulatory therapy in AD patients and indicated PRP as a potential target for future treatments in neuroinflammatory diseases like AD.
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http://dx.doi.org/10.1186/s12974-019-1520-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612126PMC
July 2019

Assessment of Psychosocial Functioning of Mothers of Children with Diabetes Mellitus Compared to Mothers of Healthy Children.

Biomed Res Int 2019 9;2019:6821575. Epub 2019 Apr 9.

Sechenov First Moscow State Medical University (Sechenov University), 119991, Moscow, Russia.

Diabetes mellitus (DM) is a chronic disease requiring changes in the behaviour of the entire family. The responsibility for implementing doctor's recommendations falls mainly upon the mother. The aim of this study is to assess the psychosocial functioning of mothers of children with DM compared to mothers of healthy children. The study involved 120 mothers: 60 with children with DM and 60 with healthy children. Data were collected using an original social-demographic questionnaire developed by the authors as well as Antonovsky's Sense of Coherence Scale (SOC-29), Schwarzer and Schultz's Berlin Social Support Scales (BSSS), Rosenberg's Self-Esteem Scale (SES), and Zigmond and Snaith's Hospital Anxiety and Depression Scale (HADS). The assessment scales were standardised and accredited by the Polish Psychological Association. The results suggest that DM in children has no effect on the psychosocial functioning of mothers regarding their self-esteem and sense of coherence. However, mothers of children with DM are well-prepared for living in a difficult situation. Social support offered to mothers of diabetic children helps them to maintain their psychosocial health.
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http://dx.doi.org/10.1155/2019/6821575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481141PMC
August 2019

Alzheimer's Disease - Future Therapy Based on Dendrimers.

Curr Neuropharmacol 2019 ;17(3):288-294

Institute of Physiologically Active Compounds of the Russian Academy of Sciences, Moscow Region, Chernogolovka, 142432, Russian Federation.

Alzheimer's disease (AD) is characterized by the loss of neurons. It is the most common cause of dementia in the elderly population accompanied by pathological degeneration of neurofibrillary tangles. Senile plaques are formed with beta-amyloid, hyperphosphoryled tau protein, apolipoprotein E and presenilin associated with protease activity [amyloid beta (Aβ), gamma-secretase (γS)]. The molecular mechanisms of neurodegeneration include apoptosis, oxidative stress (free radical generation), inflammation, immune activation, and others. The lack of effective treatments for AD stems mainly from the incomplete understanding the causes of AD. Currently, there are several hypotheses explaining the early mechanisms of AD pathogenesis. Recent years witnessed an unprecedented research growth in the area of nanotechnology, which uses atomic, molecular and macromolecular methods to create products in microscale (nanoscale) dimensions. In this article, we have discussed the role of nanotechnology in the development and improvement of techniques for early diagnosis and effective treatment of AD. Since AD pathology is practically irreversible, applications of disease-modifying treatments could be successful only if early diagnosis of AD is available. This review highlights various possibilities for the early diagnosis and therapy of AD and investigates potential adaptation of nanoparticles-dendrimers as a class of well-defined branched polymers that are chemically synthesized with a well-defined shape, size and nanoscopic physicochemical properties reminiscent of the proteins for the treatment of neurodegenerative diseases.
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http://dx.doi.org/10.2174/1570159X16666180918164623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425077PMC
June 2019

The Gut Microbiome Alterations and Inflammation-Driven Pathogenesis of Alzheimer's Disease-a Critical Review.

Mol Neurobiol 2019 Mar 23;56(3):1841-1851. Epub 2018 Jun 23.

Department of Psychiatry, Wroclaw Medical University, Wroclaw, Poland.

One of the most important scientific discoveries of recent years was the disclosure that the intestinal microflora takes part in bidirectional communication between the gut and the brain. Scientists suggest that human gut microflora may even act as the "second brain" and be responsible for neurodegenerative disorders like Alzheimer's disease (AD). Although human-associated microbial communities are generally stable, they can be altered by common human actions and experiences. Enteric bacteria, commensal, and pathogenic microorganisms, may have a major impact on immune system, brain development, and behavior, as they are able to produce several neurotransmitters and neuromodulators like serotonin, kynurenine, catecholamine, etc., as well as amyloids. However, brain destructive mechanisms, that can lead to dementia and AD, start with the intestinal microbiome dysbiosis, development of local and systemic inflammation, and dysregulation of the gut-brain axis. Increased permeability of the gut epithelial barrier results in invasion of different bacteria, viruses, and their neuroactive products that support neuroinflammatory reactions in the brain. It seems that, inflammatory-infectious hypothesis of AD, with the great role of the gut microbiome, starts to gently push into the shadow the amyloid cascade hypothesis that has dominated for decades. It is strongly postulated that AD may begin in the gut, and is closely related to the imbalance of gut microbiota. This is promising area for therapeutic intervention. Modulation of gut microbiota through personalized diet or beneficial microbiota intervention, alter microbial partners and their products including amyloid protein, will probably become a new treatment for AD.
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http://dx.doi.org/10.1007/s12035-018-1188-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394610PMC
March 2019

Sleep Disorders Associated With Alzheimer's Disease: A Perspective.

Front Neurosci 2018 31;12:330. Epub 2018 May 31.

Institute of Physiologically Active Compounds of the Russian Academy of Sciences, Chernogolovka, Russia.

Sleep disturbances, as well as sleep-wake rhythm disturbances, are typical symptoms of Alzheimer's disease (AD) that may precede the other clinical signs of this neurodegenerative disease. Here, we describe clinical features of sleep disorders in AD and the relation between sleep disorders and both cognitive impairment and poor prognosis of the disease. There are difficulties of the diagnosis of sleep disorders based on sleep questionnaires, polysomnography or actigraphy in the AD patients. Typical disturbances of the neurophysiological sleep architecture in the course of the AD include deep sleep and paradoxical sleep deprivation. Among sleep disorders occurring in patients with AD, the most frequent disorders are sleep breathing disorders and restless legs syndrome. Sleep disorders may influence circadian fluctuations of the concentrations of amyloid-β in the interstitial brain fluid and in the cerebrovascular fluid related to the glymphatic brain system and production of the amyloid-β. There is accumulating evidence suggesting that disordered sleep contributes to cognitive decline and the development of AD pathology. In this mini-review, we highlight and discuss the association between sleep disorders and AD.
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http://dx.doi.org/10.3389/fnins.2018.00330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5990625PMC
May 2018

The diabetic brain and cognition.

J Neural Transm (Vienna) 2017 11 1;124(11):1431-1454. Epub 2017 Aug 1.

The Center for Successful Aging with Diabetes, Endocrinology Institute, Gertner Institute, Sheba Medical Center, Epidemiology D., Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

The prevalence of both Alzheimer's disease (AD) and vascular dementia (VaD) is increasing with the aging of the population. Studies from the last several years have shown that people with diabetes have an increased risk for dementia and cognitive impairment. Therefore, the authors of this consensus review tried to elaborate on the role of diabetes, especially diabetes type 2 (T2DM) in both AD and VaD. Based on the clinical and experimental work of scientists from 18 countries participating in the International Congress on Vascular Disorders and on literature search using PUBMED, it can be concluded that T2DM is a risk factor for both, AD and VaD, based on a pathology of glucose utilization. This pathology is the consequence of a disturbance of insulin-related mechanisms leading to brain insulin resistance. Although the underlying pathological mechanisms for AD and VaD are different in many aspects, the contribution of T2DM and insulin resistant brain state (IRBS) to cerebrovascular disturbances in both disorders cannot be neglected. Therefore, early diagnosis of metabolic parameters including those relevant for T2DM is required. Moreover, it is possible that therapeutic options utilized today for diabetes treatment may also have an effect on the risk for dementia. T2DM/IRBS contribute to pathological processes in AD and VaD.
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http://dx.doi.org/10.1007/s00702-017-1763-2DOI Listing
November 2017

Association between Periodontal Health Status and Cognitive Abilities. The Role of Cytokine Profile and Systemic Inflammation.

Curr Alzheimer Res 2017 ;14(9):978-990

Department of Psychiatry, Wroclaw Medical University, Wroclaw. Poland.

Background: Contemporary neurobiology, periodontal medicine, and immunology are now focusing on the relationship between chronic periodontitis and systemic diseases, which also include Alzheimer's disease (AD). However a causative relationship between dementia and periodontitis has yet to be confirmed.

Objective: The aim of the study was to determine whether periodontal health status and cognitive abilities are correlated with the relative changes in systemic measures of pro- and anti-inflammatory cytokines as a reflection of systemic inflammation. We hypothesized that poor periodontal health status may be associated with cognitive impairment and dementia via the exacerbation of systemic inflammation.

Methods: Based on the periodontal and psychiatric examinations and the cytokine levels produced by unstimulated and LPS-stimulated PBL isolated from 128 participants, we have examined if the coexisting of these two clinically described conditions may have influence on the systemic inflammation. Mini- Mental State Examination (MMSE) and Bleeding on Probing (BoP) test results were combined into the one mathematical function U, which determines the severity of specific condition, called Cognitive and periodontal impairment state. Similarly, the levels of cytokines were combined into the one mathematical function V, whose value determines the level of Inflammatory state. The correlation between U and V was determined.

Results: These results confirm that the presence of cognitive decline and the additional source of proinflammatory mediators, like periodontal health problems, aggravate the systemic inflammation.

Conclusion: It is most likely that the comorbidity of these two disorders may deepen the cognitive impairment, and neurodegenerative lesions and advance to dementia and AD.
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http://dx.doi.org/10.2174/1567205014666170316163340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676025PMC
May 2018

The Infectious Etiology of Alzheimer's Disease.

Curr Neuropharmacol 2017 ;15(7):996-1009

Department of Psychiatry, Wroclaw Medical University, Wroclaw. Poland.

Background: Inflammation is a part of the first line of defense of the body against invasive pathogens, and plays a crucial role in tissue regeneration and repair. A proper inflammatory response ensures the suitable resolution of inflammation and elimination of harmful stimuli, but when the inflammatory reactions are inappropriate it can lead to damage of the surrounding normal cells. The relationship between infections and Alzheimer's Disease (AD) etiology, especially lateonset AD (LOAD) has been continuously debated over the past three decades.

Methods: This review discusses whether infections could be a causative factor that promotes the progression of AD and summarizes recent investigations associating infectious agents and chronic inflammation with AD. Preventive and therapeutic approaches to AD in the context of an infectious etiology of the disease are also discussed.

Results: Emerging evidence supports the hypothesis of the role of neurotropic viruses from the Herpesviridae family, especially Human herpesvirus 1 (HHV-1), Cytomegalovirus (CMV), and Human herpesvirus 2 (HHV-2), in AD neuropathology. Recent investigations also indicate the association between Hepatitis C virus (HCV) infection and dementia. Among bacteria special attention is focused on spirochetes family and on periodontal pathogens such as Porphyromonas gingivalis or Treponema denticola that could cause chronic periodontitis and possibly contribute to the clinical onset of AD.

Conclusion: Chronic viral, bacterial and fungal infections might be causative factors for the inflammatory pathway in AD.
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http://dx.doi.org/10.2174/1570159X15666170313122937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652018PMC
May 2018

RAGE-TLR Crosstalk Sustains Chronic Inflammation in Neurodegeneration.

Mol Neurobiol 2018 02 6;55(2):1463-1476. Epub 2017 Feb 6.

Clinic of Psychiatry, Wrocław Medical University, Pasteura 10, 50-367, Wrocław, Poland.

Chronic inflammatory reactions are consistenly present in neurodegeneration of Alzheimer type and are considered important factors that accelerate progression of the disease. Receptors of innate immunity participate in triggering and driving inflammatory reactions. For example, Toll-like receptors (TLRs) and receptor for advanced glycation end product (RAGE), major receptors of innate immunity, play a central role in perpetuation of inflammation. RAGE activation should be perceived as a primary mechanism which determines self-perpetuated chronic inflammation, and RAGE cooperation with TLRs amplifies inflammatory signaling. In this review, we highlight and discuss that RAGE-TLR crosstalk emerges as an important driving force of chronic inflammation in Alzheimer's disease.
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http://dx.doi.org/10.1007/s12035-017-0419-4DOI Listing
February 2018

Nanotechnology for Alzheimer Disease.

Curr Alzheimer Res 2017 ;14(11):1182-1189

"GALLY" International Biomedical Research Consulting LLC, San Antonio, TX 78229. United States.

Background: Alzheimer disease (AD) typically affects behavior, memory and thinking. The change in brain have been reported to begin approx. 10-20 years before the appearance of actual symptoms and diagnosis of AD. An early stage diagnosis and treatment of this lethal disease is the prime challenge, which is mainly halted by the lack of validated biomarkers.

Method: Recent nanotechnological advancements have the potential to offer large scale effective diagnostic and therapeutic options. Targeted drug (e.g. Rivastigmine) delivery with the help of nanoparticles (NPs) in the range of 1-100 nm diameters can effectively cross the blood brain barrier with minimized side effects. Moreover, biocompatible nanomaterials with increased magnetic and optical properties can act as excellent alternative agents for an early diagnosis. With the high volume of research coming in support of the effective usage of NP based drug delivery in critical environment of CNS, it is quite likely that this approach can end up providing remarkable breakthroughs in early stage diagnosis and therapy of AD.

Conclusion: In the current review, we have presented a comprehensive outlook on the current challenges in diagnosis and therapy of AD, with an emphasis on the effective options provided by biocompatible NPs as imaging contrast agents and drug carriers.
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http://dx.doi.org/10.2174/1567205014666170203125008DOI Listing
June 2018

Gliomas: New Perspectives in Diagnosis, Treatment and Prognosis.

Curr Top Med Chem 2017 ;17(12):1438-1447

GALLY International Biomedical Research Consulting LLC., 7733 Louis Pasteur Drive, #330, San Antonio, TX, 78229, United States.

Gliomas are central nervous system tumors originated from glial cells, whose incidence and mortality is expected to rise in coming years, especially in developing countries. Diagnosis and classification of gliomas have largely relied on tumor histopathologic features that provide limited information regarding response to therapy or prognosis. Current treatment of gliomas is surgery combined with chemotherapy and/or radiotherapy. However, many tumors show a high resistance to these interventions, and recurrences are frequent since conventional therapies do not take into account the unique molecular features of different subtypes of glioma. Molecular genetics provide new insights in classifying gliomas and predicting response to therapy that can range from conventional treatments to new revolutionary therapeutic approaches. This article offers a review of the intracellular signaling pathways involved in carcinogenesis of gliomas, as well as a description of new tools for their diagnosis, prognosis, and treatment with a target-oriented approach.
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http://dx.doi.org/10.2174/1568026617666170103162639DOI Listing
July 2017

Insulin Resistance in Alzheimer Disease: p53 and MicroRNAs as Important Players.

Curr Top Med Chem 2017 ;17(12):1429-1437

GALLY International Biomedical Research Consulting LLC., 7733 Louis Pasteur Drive, #330, San Antonio, TX, 78229. United States.

Glucose homeostasis is crucial for neuronal survival, synaptic plasticity, and is indispensable for learning and memory. Reduced sensitivity of cells to insulin and impaired insulin signaling in brain neurons participate in the pathogenesis of Alzheimer disease (AD). The tumor suppressor protein p53 coordinates with multiple cellular pathways in response to DNA damage and cellular stresses. However, prolonged stress conditions unveil deleterious effects of p53-evoked insulin resistance in neurons; enhancement of transcription of pro-oxidant factors, accumulation of toxic metabolites (e.g. ceramide and products of advanced glycation) and ROS-modified cellular components, together with the activation of proapoptotic genes, could finally induce a suicide death program of autophagy/apoptosis in neurons. Recent studies reveal the impact of p53 on expression and processing of several microRNAs (miRs) under DNA damage-inducing conditions. Additionally, the role of miRs in promotion of insulin resistance and type 2 diabetes mellitus has been well documented. Detailed recognition of the role of p53/miRs crosstalk in driving insulin resistance in AD brains could improve the disease diagnostics and aid future therapy.
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http://dx.doi.org/10.2174/1568026617666170103161233DOI Listing
July 2017

Type 3 Diabetes Mellitus: A Novel Implication of Alzheimers Disease.

Curr Top Med Chem 2017 ;17(12):1331-1335

GALLY International Biomedical Research Consulting LLC., 7733 Louis Pasteur Drive, #330, San Antonio, TX, 78229. United States.

The brain of patients with Alzheimer disease (AD) showed the evidence of reduced expression of insulin and neuronal insulin receptors, as compared with those of age-matched controls. This event gradually and certainly leads to a breakdown of the entire insulin-signaling pathway, which manifests insulin resistance. This in turn affects brain metabolism and cognitive functions, which are the bestdocumented abnormalities in AD. These observations led Dr. de la Monte and her colleagues to suggest that AD is actually a neuroendocrine disorder that resembles type 2 diabetes mellitus. The truth would be more complex with understanding the role of low-density lipoprotein receptor-related protein 1, Aβ derived diffusible ligands, and advanced glycation end products. However, now it known as "brain diabetes" and is called type 3 diabetes mellitus (T3DM). This review provides an overview of "brain diabetes" focusing on the reason why the phenomenon is called T3DM.
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http://dx.doi.org/10.2174/1568026617666170103163403DOI Listing
July 2017

Inflammatory Response in the CNS: Friend or Foe?

Mol Neurobiol 2017 12 26;54(10):8071-8089. Epub 2016 Nov 26.

Department of Psychiatry, Wroclaw Medical University, Wybrzeże L. Pasteura 10, 50-367, Wroclaw, Poland.

Inflammatory reactions could be both beneficial and detrimental to the brain, depending on strengths of their activation in various stages of neurodegeneration. Mild activation of microglia and astrocytes usually reveals neuroprotective effects and ameliorates early symptoms of neurodegeneration; for instance, released cytokines help maintain synaptic plasticity and modulate neuronal excitability, and stimulated toll-like receptors (TLRs) promote neurogenesis and neurite outgrowth. However, strong activation of glial cells gives rise to cytokine overexpression/dysregulation, which accelerates neurodegeneration. Altered mutual regulation of p53 protein, a major tumor suppressor, and NF-κB, the major regulator of inflammation, seems to be crucial for the shift from beneficial to detrimental effects of neuroinflammatory reactions in neurodegeneration. Therapeutic intervention in the p53-NF-κB axis and modulation of TLR activity are future challenges to cope with neurodegeneration.
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http://dx.doi.org/10.1007/s12035-016-0297-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684251PMC
December 2017

Late-life Depression and Alzheimer Disease: A Potential Synergy of the Underlying Mechanisms.

Curr Med Chem 2018 ;25(39):5389-5394

Sechenov First Moscow State Medical University, 119991, Moscow, Russian Federation.

A number of biological and clinical characteristics typical of late life depression (LLD) have been suggested by recent research findings. The close association of LLD with cognitive impairment is now well documented and evidenced. However, it is still not clear whether it is depression that leads to cognitive decline, and in more severe cases, to dementia. The work presented in this review article suggests that depression and dementia frequently and strongly copresent, even if the causality remains largely opaque.
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http://dx.doi.org/10.2174/0929867323666160902152829DOI Listing
February 2019

Inflammatory Mechanisms and Oxidative Stress as Key Factors Responsible for Progression of Neurodegeneration: Role of Brain Innate Immune System.

CNS Neurol Disord Drug Targets 2016 ;15(3):329-36

"GALLY" International Biomedical Research Consulting LLC, San Antonio, TX 78229, USA.

Chronic inflammation is characterized by longstanding microglial activation followed by sustained release of inflammatory mediators, which aid in enhanced nitrosative and oxidative stress. The sustained release of inflammatory mediators propels the inflammatory cycle by increased microglial activation, promoting their proliferation and thus stimulating enhanced release of inflammatory factors. Elevated levels of several cytokines and chronic neuroinflammation have been associated with many neurodegenerative disorders of central nervous system like age-related macular degeneration, Alzheimer disease, multiple sclerosis, Parkinson's disease, Huntington' disease, and tauopathies. This review highlights the basic mechanisms of neuroinflammation, the characteristics of neurodegenerative diseases, and the main immunologic responses in CNS neurodegenerative disorders. A comprehensive outline for the crucial role of microglia in neuroinflammation and neurodegeneration and the role of Toll-like receptor signalling in coexistence of inflammatory mechanisms and oxidative stress as major factors responsible for progression of neurodegeneration have also been presented.
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http://dx.doi.org/10.2174/1871527315666160202125914DOI Listing
December 2016

The progressive nature of concentration camp syndrome in former prisoners of Nazi concentration camps--Not just history, but the important issue of contemporary medicine.

J Psychiatr Res 2016 Apr 24;75:1-6. Epub 2015 Dec 24.

Department of Internal Medicine, Geriatrics and Allergology, Wroclaw Medical University, Marii Skłodowskiej-Curie 66 Street, 50-369 Wroclaw, Poland. Electronic address:

Constant stress, slave labor, tortures, and starvation all affected the health of concentration camp prisoners, contributing to multimorbidities, increased mortality and accelerated development of chronic illnesses, what we have shown in an earlier publication. The interrelated somatic and psychological symptoms gave rise to concentration camp syndrome (KZ-syndrome), which has many features of PTSD, occurring frequently nowadays. The paper attempts at assessing the influence of concentration camp conditions on functional disorders in each system of the human body, occurring in KZ-syndrome, and at demonstrating the progressive nature of the syndrome. A retrospective assessment of the former prisoners' health after 5 and 30 years following their leaving camps was performed based on medical records and surveys. The materials included 250 former prisoners who underwent medical examination in 1950, i.e. 5 years after leaving the camp, of whom 120 former prisoners survived and were examined and surveyed in 1975, i.e. 30 years after leaving the camp. KZ-syndrome was shown to occur in 58.8% of former prisoners 5 years after leaving the camp, and in 77.5% after 30 years (p < 0.001), which confirms the syndrome's chronic and progressive nature. Pathological sequels of internment in concentration camps, in the form of KZ-syndrome, were observed in most former prisoners. Over time, the number of morbidities and the intensity of symptoms increased, which indicates that the syndrome has a chronic and progressive nature. KZ-syndrome is a multi-organ disorder, with numerous chronic comorbidities exacerbating the progression.
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http://dx.doi.org/10.1016/j.jpsychires.2015.12.017DOI Listing
April 2016

The Innate Immunity in Alzheimer Disease- Relevance to Pathogenesis and Therapy.

Curr Pharm Des 2015 ;21(25):3582-8

"GALLY" International Biomedical Research Consulting LLC, San Antonio, TX 78229, USA.

The genetic, cellular, and molecular changes associated with Alzheimer disease provide evidence of immune and inflammatory processes involvement in its pathogenesis. These are supported by epidemiological studies, which show some benefit of long-term use of NSAID. The hypothesis that AD is in fact an immunologically mediated and even inflammatory pathological process may be in fact scientifically intriguing. There are several obstacles that suggest the need for more complex view, in the process of targeting inflammation and immunity in AD. In our previous studies we proposed a reliable methodology to assess innate immunity in Alzheimer patients and controls. The methodology is based on the phenomenon of human leukocytes being resistant to viral infection. The unspecific character of the resistance, dependent on interferons and tumor necrosis factor, and occurrence in cells ex vivo indicate that an in vivo mechanism of innate immunity may be involved. The above mentioned resistance could be estimated in a test based on peripheral blood leukocytes infection by vesicular stomachs virus.
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http://dx.doi.org/10.2174/1381612821666150710144829DOI Listing
June 2016

Impact of incarceration in Nazi concentration camps on multimorbidity of former prisoners.

Neuropsychiatr Dis Treat 2015 11;11:669-74. Epub 2015 Mar 11.

Department and Clinic of Internal Diseases, Geriatry and Allergology, Wroclaw Medical University, Wroclaw, Poland.

Objective: To show the extent to which the health of former prisoners was affected by incarceration in extermination camps after 5 and 30 years of leaving the camp, and to determine the etiological factors underlying particular dysfunctions.

Methods: Medical records of former prisoners developed in 1950 (n=250) and 1975 (n=120) were then, after several decades, retrospectively analyzed and compared with the control group, randomized and matched according to age, sex, occupation, and environment. None of the subjects in the control group was a prisoner either at a concentration camp or at any other prison or detention facility.

Results: Multimorbidity affected mainly the central nervous system (CNS). Five years after leaving a camp, CNS dysfunctions were observed in 66% of former prisoners. Skeletal (42.4%) and cardiovascular system (34.4%) dysfunctions were the second and third most frequent dysfunctions. Thirty years after leaving a camp, the most prevalent coexisting conditions were also found within the CNS (80%), cardiovascular system (58.33%), and skeletal system (55%). Five and 30 years after leaving a camp, multiorgan lesions were found in 21.6% and 60% of survivors, respectively. Multimorbidity was more frequent in a group of prisoners who underwent the state of apathy and depression or who had been incarcerated longer than 24 months. The rate of CNS diseases was four times higher, and the rate of cardiovascular diseases or skeletal system dysfunctions was two times higher, in the study group after 30 years of leaving a camp compared with the control group.

Conclusion: The consequences of incarceration in concentration camps manifesting as multimorbidity, premature aging, and dramatic increase in mortality rate are observed in the majority of former prisoners. The multimorbidity mostly affected older prisoners who stayed at a camp for a longer time period.
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http://dx.doi.org/10.2147/NDT.S76944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362975PMC
March 2015

Evaluation of the posterior cingulate region with FDG-PET and advanced MR techniques in patients with amnestic mild cognitive impairment: comparison of the methods.

J Alzheimers Dis 2015 ;44(1):329-38

Department of General and Interventional Radiology and Neuroradiology, Wroclaw Medical University, Wroclaw, Poland Euromedic Wroclaw PET/CT Medical Center, Wroclaw, Poland.

Background: The posterior cingulate region is an area of the earliest pathological changes in amnestic mild cognitive impairment (aMCI). The utility of FDG-PET imaging in dementia is already well established.

Objectives: The aim of the study was to compare FDG-PET with advanced MR measurements: MR spectroscopy (MRS), perfusion weighted imaging (PWI), and diffusion tensor imaging (DTI) within the posterior cingulate region in patients with aMCI.

Methods: Fifty-five patients diagnosed with aMCI (66.5 y) and 20 age-matched controls (69 y) underwent MR examination including MRS, PWI, and DTI followed by FDG-PET scanning. Values of MRS metabolite ratios (NAA/Cr, Cho/Cr, mI/Cr), PWI cerebral blood volume (rCBV), and DTI fractional anisotropy (FA) were compared to the FDG-PET rates of glucose metabolism.

Results: Compared to controls, aMCI patients showed significant (p < 0.05) glucose hypometabolism, and lower rCBV and FA values. FDG-PET results correlated significantly with rCBV values. Compared to FDG-PET, PWI showed similar and DTI greater accuracy in distinguishing aMCI from controls. According to FDG-PET findings, two groups of aMCI patients were established: those with lower (PET-positive) and normal (PET-negative) glucose uptake. PET-positive aMCI subjects showed normal MRS findings, lower rCBV and FA values, while PET-negative patients revealed normal MRS and PWI results but significantly lower FA values.

Conclusions: Advanced MR techniques such as PWI and particularly DTI may be regarded as competitive techniques to FDG-PET. DTI was the only method to show alterations in aMCI patients with normal FDG-PET, PWI, and MRS findings. DTI seems to be a very sensitive biomarker of early degeneration in aMCI.
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http://dx.doi.org/10.3233/JAD-132138DOI Listing
September 2015

[The importance of folic acid deficiency in the pathogenesis of vascular, mixed and Alzheimer's disease dementia].

Pol Merkur Lekarski 2013 Oct;35(208):205-9

Department of Psychiatry, Medical University of Wroclaw, Poland.

Unlabelled: Alzheimer's disease (AD), vascular dementia (VaD) and mixed dementia (MD) are the most common dementia diseases among the elderly. Currently, there is no effective treatment of these diseases and, therefore, it seems justified to develop the principles of prevention, taking into account the elimination of risk factors. Among them folic acid deficiency may play an important role.

The Aim Of The Study: To evaluate possible relationship of folate deficiency with the development of selected dementia diseases: vascular dementia (VaD), Alzheimer's disease (AD), mixed dementia (MD).

Material And Methods: The study involved 166 people, including 47 people with the diagnosis of AD, 41 with VaD and 36 with MD. The control group consisted of 42 persons without cognitive impairment. All patients underwent a general physical, neurological, psychiatric and extensive neuropsychological examination, as well as routine blood and biochemical screening tests and neuroimaging. The level of serum folate (Fol) was measured by electrochemiluminescence immunoassay. To assess the correlation of Fol level with the cognitive impairment neuropsychometric scales: Mini Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) were used.

Results: In patients with dementia, compared with the control group, there were significantly lower levels of folic acid (p = 0.04). There was no difference in the concentration of Fol in groups of patients (p = 0.0889). In people without cognitive impairment (CDR 0) levels of folic acid were significantly higher compared to the group with moderate dementia (CDR 2, p = 0.0475).

Conclusions: The results may suggest that folic acid deficiency is one of the possible causes of dementia, but does not determine its type. Determination of serum Fol in the elderly and supplementation of this vitamin deficiency may play an important role in the prevention of the most common dementias.
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October 2013