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Special Issue "Epigenetic Regulation in Neurodegeneration Disease"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 31 May 2021.

Special Issue Editor

Dr. Laszlo Bodai
E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology,University of Szeged, ‎Szeged, Hungary
Interests: Molecular pathogenesis of Huntington’s disease; epigenetic regulation of transcription, the biological role of histone variants and histone modifications

Special Issue Information

Dear Colleagues,

Neurodegeneration disorders are devastating diseases that cause symptoms ranging from movement and psychiatric disturbances to cognitive decline and might have fatal consequences. Despite decades of intensive research, an effective cure is not available for most neurodegenerative diseases; therefore, a better understanding of the molecular basis of their pathogenesis is imperative. Despite the diversity of affected brain structures and the multifaceted pathogenesis, some pathological processes seem to be common for several neurodegenerative disorders. One of these pathogenic mechanisms is epigenetic dysregulation, an alteration in the structure and functional state of chromatin that can be the consequence of altered DNA methylation patterns, or dysregulated histone post-translational modifications, among others. As the state of chromatin regulates all DNA-templated processes, including gene transcription, it has widespread effects on various cellular mechanisms. The aim of this Special Issue is to shed light on recent advances in research into the epigenetic background of neurodegenerative disorders and the potential applicability of epigenetic therapy. For this Special Issue, we welcome the following manuscript categories: original scientific research articles, short communications, and review articles.

Dr. Laszlo Bodai
Guest Editor

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 papers will be 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 
  • neurodegenerative disorders 
  • Alzheimer’s disease 
  • Parkinson’s disease 
  • polyglutamine diseases 
  • epigenetics 
  • chromatin 
  • histone modifications 
  • DNA methylation 
  • chromatin remodeling

Published Papers (3 papers)

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Research

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Open AccessArticle
Knock-Down of HDAC2 in Human Induced Pluripotent Stem Cell Derived Neurons Improves Neuronal Mitochondrial Dynamics, Neuronal Maturation and Reduces Amyloid Beta Peptides
Int. J. Mol. Sci. 2021, 22(5), 2526; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052526 - 03 Mar 2021
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Abstract
Histone deacetylase 2 (HDAC2) is a major HDAC protein in the adult brain and has been shown to regulate many neuronal genes. The aberrant expression of HDAC2 and subsequent dysregulation of neuronal gene expression is implicated in neurodegeneration and brain aging. Human induced [...] Read more.
Histone deacetylase 2 (HDAC2) is a major HDAC protein in the adult brain and has been shown to regulate many neuronal genes. The aberrant expression of HDAC2 and subsequent dysregulation of neuronal gene expression is implicated in neurodegeneration and brain aging. Human induced pluripotent stem cell-derived neurons (hiPSC-Ns) are widely used models for studying neurodegenerative disease mechanisms, but the role of HDAC2 in hiPSC-N differentiation and maturation has not been explored. In this study, we show that levels of HDAC2 progressively decrease as hiPSCs are differentiated towards neurons. This suppression of HDAC2 inversely corresponds to an increase in neuron-specific isoforms of Endophilin-B1, a multifunctional protein involved in mitochondrial dynamics. Expression of neuron-specific isoforms of Endophilin-B1 is accompanied by concomitant expression of a neuron-specific alternative splicing factor, SRRM4. Manipulation of HDAC2 and Endophilin-B1 using lentiviral approaches shows that the knock-down of HDAC2 or the overexpression of a neuron-specific Endophilin-B1 isoform promotes mitochondrial elongation and protects against cytotoxic stress in hiPSC-Ns, while HDAC2 knock-down specifically influences genes regulating mitochondrial dynamics and synaptogenesis. Furthermore, HDAC2 knock-down promotes enhanced mitochondrial respiration and reduces levels of neurotoxic amyloid beta peptides. Collectively, our study demonstrates a role for HDAC2 in hiPSC-neuronal differentiation, highlights neuron-specific isoforms of Endophilin-B1 as a marker of differentiating hiPSC-Ns and demonstrates that HDAC2 regulates key neuronal and mitochondrial pathways in hiPSC-Ns. Full article
(This article belongs to the Special Issue Epigenetic Regulation in Neurodegeneration Disease)
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Open AccessArticle
Nuclear Reorganization in Hippocampal Granule Cell Neurons from a Mouse Model of Down Syndrome: Changes in Chromatin Configuration, Nucleoli and Cajal Bodies
Int. J. Mol. Sci. 2021, 22(3), 1259; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031259 - 27 Jan 2021
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Abstract
Down syndrome (DS) or trisomy of chromosome 21 (Hsa21) is characterized by impaired hippocampal-dependent learning and memory. These alterations are due to defective neurogenesis and to neuromorphological and functional anomalies of numerous neuronal populations, including hippocampal granular cells (GCs). It has been proposed [...] Read more.
Down syndrome (DS) or trisomy of chromosome 21 (Hsa21) is characterized by impaired hippocampal-dependent learning and memory. These alterations are due to defective neurogenesis and to neuromorphological and functional anomalies of numerous neuronal populations, including hippocampal granular cells (GCs). It has been proposed that the additional gene dose in trisomic cells induces modifications in nuclear compartments and on the chromatin landscape, which could contribute to some DS phenotypes. The Ts65Dn (TS) mouse model of DS carries a triplication of 92 genes orthologous to those found in Hsa21, and shares many phenotypes with DS individuals, including cognitive and neuromorphological alterations. Considering its essential role in hippocampal memory formation, we investigated whether the triplication of this set of Hsa21 orthologous genes in TS mice modifies the nuclear architecture of their GCs. Our results show that the TS mouse presents alterations in the nuclear architecture of its GCs, affecting nuclear compartments involved in transcription and pre-rRNA and pre-mRNA processing. In particular, the GCs of the TS mouse show alterations in the nucleolar fusion pattern and the molecular assembly of Cajal bodies (CBs). Furthermore, hippocampal GCs of TS mice present an epigenetic dysregulation of chromatin that results in an increased heterochromatinization and reduced global transcriptional activity. These nuclear alterations could play an important role in the neuromorphological and/or functional alterations of the hippocampal GCs implicated in the cognitive dysfunction characteristic of TS mice. Full article
(This article belongs to the Special Issue Epigenetic Regulation in Neurodegeneration Disease)
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Review

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Open AccessReview
Histone Methylation Regulation in Neurodegenerative Disorders
Int. J. Mol. Sci. 2021, 22(9), 4654; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094654 - 28 Apr 2021
Viewed by 255
Abstract
Advances achieved with molecular biology and genomics technologies have permitted investigators to discover epigenetic mechanisms, such as DNA methylation and histone posttranslational modifications, which are critical for gene expression in almost all tissues and in brain health and disease. These advances have influenced [...] Read more.
Advances achieved with molecular biology and genomics technologies have permitted investigators to discover epigenetic mechanisms, such as DNA methylation and histone posttranslational modifications, which are critical for gene expression in almost all tissues and in brain health and disease. These advances have influenced much interest in understanding the dysregulation of epigenetic mechanisms in neurodegenerative disorders. Although these disorders diverge in their fundamental causes and pathophysiology, several involve the dysregulation of histone methylation-mediated gene expression. Interestingly, epigenetic remodeling via histone methylation in specific brain regions has been suggested to play a critical function in the neurobiology of psychiatric disorders, including that related to neurodegenerative diseases. Prominently, epigenetic dysregulation currently brings considerable interest as an essential player in neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS) and drugs of abuse, including alcohol abuse disorder, where it may facilitate connections between genetic and environmental risk factors or directly influence disease-specific pathological factors. We have discussed the current state of histone methylation, therapeutic strategies, and future perspectives for these disorders. While not somatically heritable, the enzymes responsible for histone methylation regulation, such as histone methyltransferases and demethylases in neurons, are dynamic and reversible. They have become promising potential therapeutic targets to treat or prevent several neurodegenerative disorders. These findings, along with clinical data, may provide links between molecular-level changes and behavioral differences and provide novel avenues through which the epigenome may be targeted early on in people at risk for neurodegenerative disorders. Full article
(This article belongs to the Special Issue Epigenetic Regulation in Neurodegeneration Disease)
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