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Brain Sciences
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New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders
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New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Molecular and Cellular Neuroscience".

Deadline for manuscript submissions: closed (2 July 2022) | Viewed by 46333

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Prof. Dr. Christina Piperi

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Guest Editor
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
Interests: neuroinflammation; neuro-oncology; neurodegeneration; epigenetics; histone modifications; signal transduction; transcription factors
Special Issues, Collections and Topics in MDPI journals
Dr. Chiara Villa

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
Interests: genetics; Alzheimer’s disease; non-coding RNAs; neurodegeneration; epilepsy; brain; biomarkers
Special Issues, Collections and Topics in MDPI journals
Dr. Yam Nath Paudel

E-Mail Website
Guest Editor
Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Malaysia
Interests: Neurodegeneration; Neurological disorders; HMGB1 protein; Epilepsy; Parkinson disease; Alzheimer disease

Special Issue Information

Dear Colleagues,

Neurodegenerative disorders encompass a broad range of sporadic and/or familial debilitating conditions characterized by the progressive dysfunction and loss of selective neuronal populations, determining different clinical phenotypes. Emerging research data indicate an interplay of genetic factors and epigenetic mechanisms underlying neurodegenerative processes, which lead to increased prevalence of neurodegenerative disorders. In concert with the constant increase in the aging population, neurodegenerative disorders currently represent a major challenge to public health worldwide.

Despite recent advances in clinical and preclinical research, the pathogenesis of these disorders still remains poorly understood, without effective treatments being available to halt the neurodegenerative processes, but rather aiming at relieving symptoms. Therefore, a critical evaluation of current research data and in depth understanding of the molecular mechanisms that lead to neurodegeneration is crucial in order to identify potential therapeutic targets that can pave the way to the development of novel and promising therapies.

This Special Issue is focused on novel molecular data in the field of neurodegeneration that associate with the onset and progression of neurodegenerative diseases. We are particularly interested in original articles and reviews that provide new insights into the main molecular pathogenic mechanisms underlying neurodegenerative disorders, aiming to identify potential biomarkers and novel therapeutic strategies.

Prof. Dr. Christina Piperi
Dr. Chiara Villa
Dr. Yam Nath Paudel
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neurodegeneration
  • Alzheimer’s disease 
  • Parkinson’s disease 
  • amyotrophic lateral sclerosis 
  • multiple sclerosis 
  • Huntington’s disease 
  • motor neuron disease 
  • biomarkers

Published Papers (13 papers)

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Editorial

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3 pages, 176 KiB  
Editorial
New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders
by Chiara Villa, Yam Nath Paudel and Christina Piperi
Brain Sci. 2022, 12(9), 1190; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12091190 - 03 Sep 2022
Viewed by 1186
Abstract
Neurodegenerative disorders remain a major burden for our society, affecting millions of people worldwide [...] Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)

Research

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14 pages, 2749 KiB  
Article
Transcriptome Sequencing Reveal That Rno-Rsf1_0012 Participates in Levodopa-Induced Dyskinesia in Parkinson’s Disease Rats via Binding to Rno-mir-298-5p
by Chun-Lei Han, Qiao Wang, Chong Liu, Zhi-Bao Li, Ting-Ting Du, Yun-Peng Sui, Xin Zhang, Jian-Guo Zhang, Yi-Lei Xiao, Guo-En Cai and Fan-Gang Meng
Brain Sci. 2022, 12(9), 1206; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12091206 - 07 Sep 2022
Cited by 1 | Viewed by 1461
Abstract
Levodopa-induced dyskinesia (LID) is a common complication of chronic dopamine replacement therapy in the treatment of Parkinson’s disease (PD), and a noble cause of disability in advanced PD patients. Circular RNA (circRNA) is a novel type of non-coding RNA with a covalently closed-loop [...] Read more.
Levodopa-induced dyskinesia (LID) is a common complication of chronic dopamine replacement therapy in the treatment of Parkinson’s disease (PD), and a noble cause of disability in advanced PD patients. Circular RNA (circRNA) is a novel type of non-coding RNA with a covalently closed-loop structure, which can regulate gene expression and participate in many biological processes. However, the biological roles of circRNAs in LID are not completely known. In the present study, we established typical LID rat models by unilateral lesions of the medial forebrain bundle and repeated levodopa therapy. High-throughput next-generation sequencing was used to screen circRNAs differentially expressed in the brain of LID and non-LID (NLID) rats, and key circRNAs were selected according to bioinformatics analyses. Regarding fold change ≥2 and p < 0.05 as the cutoff value, there were a total of 99 differential circRNAs, including 39 up-regulated and 60 down-regulated circRNAs between the NLID and LID groups. The expression of rno-Rsf1_0012 was significantly increased in the striatum of LID rats and competitively bound rno-mir-298-5p. The high expression of target genes PCP and TBP in LID rats also supports the conclusion that rno-Rsf1_0012 may be related to the occurrence of LID. Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)
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16 pages, 2189 KiB  
Article
Changes in Tyrosine Hydroxylase Activity and Dopamine Synthesis in the Nigrostriatal System of Mice in an Acute Model of Parkinson’s Disease as a Manifestation of Neurodegeneration and Neuroplasticity
by Anna Kolacheva, Leyla Alekperova, Ekaterina Pavlova, Alyona Bannikova and Michael V. Ugrumov
Brain Sci. 2022, 12(6), 779; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12060779 - 14 Jun 2022
Cited by 10 | Viewed by 2363
Abstract
The progressive degradation of the nigrostriatal system leads to the development of Parkinson’s disease (PD). The synthesis of dopamine, the neurotransmitter of the nigrostriatal system, depends on the rate-limiting enzyme, tyrosine hydroxylase (TH). In this study, we evaluated the synthesis of dopamine during [...] Read more.
The progressive degradation of the nigrostriatal system leads to the development of Parkinson’s disease (PD). The synthesis of dopamine, the neurotransmitter of the nigrostriatal system, depends on the rate-limiting enzyme, tyrosine hydroxylase (TH). In this study, we evaluated the synthesis of dopamine during periods of neurodegradation and neuroplasticity in the nigrostriatal system on a model of the early clinical stage of PD. It was shown that the concentration of dopamine correlated with activity of TH, while TH activity did not depend on total protein content either in the SN or in the striatum. Both during the period of neurodegeneration and neuroplasticity, TH activity in SN was determined by the content of P19-TH, and in the striatum it was determined by P31-TH and P40-TH (to a lesser extent). The data obtained indicate a difference in the regulation of dopamine synthesis between DA-neuron bodies and their axons, which must be considered for the further development of symptomatic pharmacotherapy aimed at increasing TH activity. Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)
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20 pages, 5261 KiB  
Article
Homology Modelling, Molecular Docking and Molecular Dynamics Simulation Studies of CALMH1 against Secondary Metabolites of Bauhinia variegata to Treat Alzheimer’s Disease
by Noopur Khare, Sanjiv Kumar Maheshwari, Syed Mohd Danish Rizvi, Hind Muteb Albadrani, Suliman A. Alsagaby, Wael Alturaiki, Danish Iqbal, Qamar Zia, Chiara Villa, Saurabh Kumar Jha, Niraj Kumar Jha and Abhimanyu Kumar Jha
Brain Sci. 2022, 12(6), 770; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12060770 - 12 Jun 2022
Cited by 12 | Viewed by 2741
Abstract
Calcium homeostasis modulator 1 (CALHM1) is a protein responsible for causing Alzheimer’s disease. In the absence of an experimentally designed protein molecule, homology modelling was performed. Through homology modelling, different CALHM1 models were generated and validated through Rampage. To carry out further in [...] Read more.
Calcium homeostasis modulator 1 (CALHM1) is a protein responsible for causing Alzheimer’s disease. In the absence of an experimentally designed protein molecule, homology modelling was performed. Through homology modelling, different CALHM1 models were generated and validated through Rampage. To carry out further in silico studies, through molecular docking and molecular dynamics simulation experiments, various flavonoids and alkaloids from Bauhinia variegata were utilised as inhibitors to target the protein (CALHM1). The sequence of CALHM1 was retrieved from UniProt and the secondary structure prediction of CALHM1 was done through CFSSP, GOR4, and SOPMA methods. The structure was identified through LOMETS, MUSTER, and MODELLER and finally, the structures were validated through Rampage. Bauhinia variegata plant was used to check the interaction of alkaloids and flavonoids against CALHM1. The protein and protein–ligand complex were also validated through molecular dynamics simulations studies. The model generated through MODELLER software with 6VAM A was used because this model predicted the best results in the Ramachandran plot. Further molecular docking was performed, quercetin was found to be the most appropriate candidate for the protein molecule with the minimum binding energy of −12.45 kcal/mol and their ADME properties were analysed through Molsoft and Molinspiration. Molecular dynamics simulations showed that CALHM1 and CALHM1–quercetin complex became stable at 2500 ps. It may be seen through the study that quercetin may act as a good inhibitor for treatment. With the help of an in silico study, it was easier to analyse the 3D structure of the protein, which may be scrutinized for the best-predicted model. Quercetin may work as a good inhibitor for treating Alzheimer’s disease, according to in silico research using molecular docking and molecular dynamics simulations, and future in vitro and in vivo analysis may confirm its effectiveness. Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)
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12 pages, 1425 KiB  
Article
Not just a Snapshot: An Italian Longitudinal Evaluation of Stability of Gut Microbiota Findings in Parkinson’s Disease
by Rocco Cerroni, Daniele Pietrucci, Adelaide Teofani, Giovanni Chillemi, Claudio Liguori, Mariangela Pierantozzi, Valeria Unida, Sidorela Selmani, Nicola Biagio Mercuri and Alessandro Stefani
Brain Sci. 2022, 12(6), 739; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12060739 - 04 Jun 2022
Cited by 7 | Viewed by 2068
Abstract
Most research analyzed gut-microbiota alterations in Parkinson’s disease (PD) through cross-sectional studies, as single snapshots, without considering the time factor to either confirm methods and findings or observe longitudinal variations. In this study, we introduce the time factor by comparing gut-microbiota composition in [...] Read more.
Most research analyzed gut-microbiota alterations in Parkinson’s disease (PD) through cross-sectional studies, as single snapshots, without considering the time factor to either confirm methods and findings or observe longitudinal variations. In this study, we introduce the time factor by comparing gut-microbiota composition in 18 PD patients and 13 healthy controls (HC) at baseline and at least 1 year later, also considering PD clinical features. PD patients and HC underwent a fecal sampling at baseline and at a follow-up appointment. Fecal samples underwent sequencing and 16S rRNA amplicons analysis. Patients’clinical features were valued through Hoehn&Yahr (H&Y) staging-scale and Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) Part-III. Results demonstrated stability in microbiota findings in both PD patients and HC over a period of 14 months: both alfa and beta diversity were maintained in PD patients and HC over the observation period. In addition, differences in microbiota composition between PD patients and HC remained stable over the time period. Moreover, during the same period, patients did not experience any worsening of either staging or motor impairment. Our findings, highlighting the stability and reproducibility of the method, correlate clinical and microbiota stability over time and open the scenario to more extensive longitudinal evaluations. Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)
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11 pages, 3080 KiB  
Communication
Stochasticity, Entropy and Neurodegeneration
by Peter K. Panegyres
Brain Sci. 2022, 12(2), 226; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12020226 - 07 Feb 2022
Cited by 2 | Viewed by 1250
Abstract
We previously suggested that stochastic processes are fundamental in the development of sporadic adult onset neurodegenerative disorders. In this study, we develop a theoretical framework to explain stochastic processes at the protein, DNA and RNA levels. We propose that probability determines random sequencing [...] Read more.
We previously suggested that stochastic processes are fundamental in the development of sporadic adult onset neurodegenerative disorders. In this study, we develop a theoretical framework to explain stochastic processes at the protein, DNA and RNA levels. We propose that probability determines random sequencing changes, some of which favor neurodegeneration in particular anatomical spaces, and that more than one protein may be affected simultaneously. The stochastic protein changes happen in three-dimensional space and can be considered to be vectors in a space-time continuum, their trajectories and kinetics modified by physiological variables in the manifold of intra- and extra-cellular space. The molecular velocity of these degenerative proteins must obey the second law of thermodynamics, in which entropy is the driver of the inexorable progression of neurodegeneration in the context of the N-body problem of interacting proteins, time-space manifold of protein-protein interactions in phase space, and compounded by the intrinsic disorder of protein-protein networks. This model helps to elucidate the existence of multiple misfolded proteinopathies in adult sporadic neurodegenerative disorders. Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)
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12 pages, 1143 KiB  
Article
Shared Genetic Background between Parkinson’s Disease and Schizophrenia: A Two-Sample Mendelian Randomization Study
by Kiwon Kim, Soyeon Kim, Woojae Myung, Injeong Shim, Hyewon Lee, Beomsu Kim, Sung Kweon Cho, Joohyun Yoon, Doh Kwan Kim and Hong-Hee Won
Brain Sci. 2021, 11(8), 1042; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci11081042 - 06 Aug 2021
Cited by 10 | Viewed by 5060
Abstract
Background and objectives: Parkinson’s disease (PD) and schizophrenia often share symptomatology. Psychotic symptoms are prevalent in patients with PD, and similar motor symptoms with extrapyramidal signs are frequently observed in antipsychotic-naïve patients with schizophrenia as well as premorbid families. However, few studies [...] Read more.
Background and objectives: Parkinson’s disease (PD) and schizophrenia often share symptomatology. Psychotic symptoms are prevalent in patients with PD, and similar motor symptoms with extrapyramidal signs are frequently observed in antipsychotic-naïve patients with schizophrenia as well as premorbid families. However, few studies have examined the relationship between PD and schizophrenia. We performed this study to evaluate whether genetic variants which increase PD risk influence the risk of developing schizophrenia, and vice versa. Materials and Methods: Two-sample Mendelian randomization (TSMR) with summary statistics from large-scale genome-wide association studies (GWAS) was applied. Summary statistics were extracted for these instruments from GWAS of PD and schizophrenia; Results: We found an increase in the risk of schizophrenia per one-standard deviation (SD) increase in the genetically-predicted PD risk (inverse-variance weighted method, odds ratio = 1.10; 95% confidence interval, 1.05−1.15; p = 3.49 × 10−5). The association was consistent in sensitivity analyses, including multiple TSMR methods, analysis after removing outlier variants with potential pleiotropic effects, and analysis after applying multiple GWAS subthresholds. No relationships were evident between PD and smoking or other psychiatric disorders, including attention deficit hyperactivity disorder, autism spectrum disorder, bipolar affective disorder, major depressive disorder, Alzheimer’s disease, or alcohol dependence. However, we did not find a reverse relationship; genetic variants increasing schizophrenia risk did not alter the risk of PD; Conclusions: Overall, our findings suggest that increased genetic risk of PD can be associated with increased risk of schizophrenia. This association supports the intrinsic nature of the psychotic symptom in PD rather than medication or environmental effects. Future studies for possible comorbidities and shared genetic structure between the two diseases are warranted. Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)
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Review

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18 pages, 882 KiB  
Review
New Insights into the Molecular Interplay between Human Herpesviruses and Alzheimer’s Disease—A Narrative Review
by Evita Athanasiou, Antonios N. Gargalionis, Cleo Anastassopoulou, Athanassios Tsakris and Fotini Boufidou
Brain Sci. 2022, 12(8), 1010; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12081010 - 30 Jul 2022
Cited by 7 | Viewed by 2476
Abstract
Human herpesviruses (HHVs) have been implicated as possible risk factors in Alzheimer’s disease (AD) pathogenesis. Persistent lifelong HHVs infections may directly or indirectly contribute to the generation of AD hallmarks: amyloid beta (Aβ) plaques, neurofibrillary tangles composed of hyperphosphorylated tau proteins, and synaptic [...] Read more.
Human herpesviruses (HHVs) have been implicated as possible risk factors in Alzheimer’s disease (AD) pathogenesis. Persistent lifelong HHVs infections may directly or indirectly contribute to the generation of AD hallmarks: amyloid beta (Aβ) plaques, neurofibrillary tangles composed of hyperphosphorylated tau proteins, and synaptic loss. The present review focuses on summarizing current knowledge on the molecular mechanistic links between HHVs and AD that include processes involved in Aβ accumulation, tau protein hyperphosphorylation, autophagy, oxidative stress, and neuroinflammation. A PubMed search was performed to collect all the available research data regarding the above mentioned mechanistic links between HHVs and AD pathology. The vast majority of research articles referred to the different pathways exploited by Herpes Simplex Virus 1 that could lead to AD pathology, while a few studies highlighted the emerging role of HHV 6, cytomegalovirus, and Epstein–Barr Virus. The elucidation of such potential links may guide the development of novel diagnostics and therapeutics to counter this devastating neurological disorder that until now remains incurable. Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)
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11 pages, 2067 KiB  
Review
Recent Advances in Progresses and Prospects of IL-37 in Central Nervous System Diseases
by Xinrui Li, Bing Yan, Jin Du, Shanshan Xu, Lu Liu, Caifei Pan, Xianhui Kang and Shengmei Zhu
Brain Sci. 2022, 12(6), 723; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12060723 - 31 May 2022
Cited by 1 | Viewed by 1937
Abstract
Interleukin-37 (IL-37) is an effective anti-inflammatory factor and acts through intracellular and extracellular pathways, inhibiting the effects of other inflammatory cytokines, such as IL-1β, IL-6, and tumor necrosis factor-α (TNF-α), thereby exerting powerful anti-inflammatory effects. In numerous recent studies, the anti-inflammatory effects of [...] Read more.
Interleukin-37 (IL-37) is an effective anti-inflammatory factor and acts through intracellular and extracellular pathways, inhibiting the effects of other inflammatory cytokines, such as IL-1β, IL-6, and tumor necrosis factor-α (TNF-α), thereby exerting powerful anti-inflammatory effects. In numerous recent studies, the anti-inflammatory effects of IL-37 have been described in many autoimmune diseases, colitis, and tumors. However, the current research on IL-37 in the field of the central nervous system (CNS) is not only less, but mainly for clinical research and little discussion of the mechanism. In this review, the role of IL-37 and its associated inflammatory factors in common CNS diseases are summarized, and their therapeutic potential in CNS diseases identified. Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)
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16 pages, 1166 KiB  
Review
Brain Connectivity and Graph Theory Analysis in Alzheimer’s and Parkinson’s Disease: The Contribution of Electrophysiological Techniques
by Francesca Miraglia, Fabrizio Vecchio, Chiara Pappalettera, Lorenzo Nucci, Maria Cotelli, Elda Judica, Florinda Ferreri and Paolo Maria Rossini
Brain Sci. 2022, 12(3), 402; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12030402 - 18 Mar 2022
Cited by 15 | Viewed by 3753
Abstract
In recent years, applications of the network science to electrophysiological data have increased as electrophysiological techniques are not only relatively low cost, largely available on the territory and non-invasive, but also potential tools for large population screening. One of the emergent methods for [...] Read more.
In recent years, applications of the network science to electrophysiological data have increased as electrophysiological techniques are not only relatively low cost, largely available on the territory and non-invasive, but also potential tools for large population screening. One of the emergent methods for the study of functional connectivity in electrophysiological recordings is graph theory: it allows to describe the brain through a mathematic model, the graph, and provides a simple representation of a complex system. As Alzheimer’s and Parkinson’s disease are associated with synaptic disruptions and changes in the strength of functional connectivity, they can be well described by functional connectivity analysis computed via graph theory. The aim of the present review is to provide an overview of the most recent applications of the graph theory to electrophysiological data in the two by far most frequent neurodegenerative disorders, Alzheimer’s and Parkinson’s diseases. Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)
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24 pages, 873 KiB  
Review
Environmental Impact on the Epigenetic Mechanisms Underlying Parkinson’s Disease Pathogenesis: A Narrative Review
by Efthalia Angelopoulou, Yam Nath Paudel, Sokratis G. Papageorgiou and Christina Piperi
Brain Sci. 2022, 12(2), 175; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci12020175 - 28 Jan 2022
Cited by 31 | Viewed by 5683
Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disorder with an unclear etiology and no disease-modifying treatment to date. PD is considered a multifactorial disease, since both genetic and environmental factors contribute to its pathogenesis, although the molecular mechanisms linking these two [...] Read more.
Parkinson’s disease (PD) is the second most common neurodegenerative disorder with an unclear etiology and no disease-modifying treatment to date. PD is considered a multifactorial disease, since both genetic and environmental factors contribute to its pathogenesis, although the molecular mechanisms linking these two key disease modifiers remain obscure. In this context, epigenetic mechanisms that alter gene expression without affecting the DNA sequence through DNA methylation, histone post-transcriptional modifications, and non-coding RNAs may represent the key mediators of the genetic–environmental interactions underlying PD pathogenesis. Environmental exposures may cause chemical alterations in several cellular functions, including gene expression. Emerging evidence has highlighted that smoking, coffee consumption, pesticide exposure, and heavy metals (manganese, arsenic, lead, etc.) may potentially affect the risk of PD development at least partially via epigenetic modifications. Herein, we discuss recent accumulating pre-clinical and clinical evidence of the impact of lifestyle and environmental factors on the epigenetic mechanisms underlying PD development, aiming to shed more light on the pathogenesis and stimulate future research. Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)
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13 pages, 10733 KiB  
Review
Is Aducanumab for LMICs? Promises and Challenges
by Illangage P. C. Gunawardena, Thaarvena Retinasamy and Mohd. Farooq Shaikh
Brain Sci. 2021, 11(11), 1547; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci11111547 - 22 Nov 2021
Cited by 5 | Viewed by 9093
Abstract
Aducanumab, a human monoclonal antibody, was approved in June of 2021 as the first disease-modifying treatment for Alzheimer’s disease by the United States Food and Drug Administration (U.S. FDA). A substantial proportion of patients with Alzheimer’s disease live in low- and middle-income countries [...] Read more.
Aducanumab, a human monoclonal antibody, was approved in June of 2021 as the first disease-modifying treatment for Alzheimer’s disease by the United States Food and Drug Administration (U.S. FDA). A substantial proportion of patients with Alzheimer’s disease live in low- and middle-income countries (LMICs), and the debilitating effects of this disease exerts burdens on patients and caregivers in addition to the significant economic strains many nations bear. While the advantages of a disease-modifying therapy are clear in delaying the progression of disease to improve patient outcomes, aducanumab’s approval by the U.S. FDA was met with controversy for a plethora of reasons. This paper will provide precursory insights into aducanumab’s role, appropriateness, and cost-effectiveness in low- and middle-income countries. We extend some of the controversies associated with aducanumab, including the contradicting evidence from the two trials (EMERGE and ENGAGE) and the resources required to deliver the treatment safely and effectively to patients, among other key considerations. Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)
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10 pages, 1805 KiB  
Review
TLR-Mediated Signal Transduction and Neurodegenerative Disorders
by Shashank Vishwanath Adhikarla, Niraj Kumar Jha, Vineet Kumar Goswami, Ankur Sharma, Anuradha Bhardwaj, Abhijit Dey, Chiara Villa, Yatender Kumar and Saurabh Kumar Jha
Brain Sci. 2021, 11(11), 1373; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci11111373 - 20 Oct 2021
Cited by 19 | Viewed by 4815
Abstract
A special class of proteins called Toll-like receptors (TLRs) are an essential part of the innate immune system, connecting it to the adaptive immune system. There are 10 different Toll-Like Receptors that have been identified in human beings. TLRs are part of the [...] Read more.
A special class of proteins called Toll-like receptors (TLRs) are an essential part of the innate immune system, connecting it to the adaptive immune system. There are 10 different Toll-Like Receptors that have been identified in human beings. TLRs are part of the central nervous system (CNS), showing that the CNS is capable of the immune response, breaking the long-held belief of the brain’s “immune privilege” owing to the blood–brain barrier (BBB). These Toll-Like Receptors are present not just on the resident macrophages of the central nervous system but are also expressed by the neurons to allow them for the production of proinflammatory agents such as interferons, cytokines, and chemokines; the activation and recruitment of glial cells; and their participation in neuronal cell death by apoptosis. This study is focused on the potential roles of various TLRs in various neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), namely TLR2, TLR3, TLR4, TLR7, and TLR9 in AD and PD in human beings and a mouse model. Full article
(This article belongs to the Special Issue New Insights into Molecular Mechanisms Underlying Neurodegenerative Disorders)
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