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Non-Cell Autonomous and Epigenetic Mechanisms of Huntington's Disease.

ABSTRACT: Huntington's disease (HD) is a rare neurodegenerative disorder caused by an expansion of CAG trinucleotide repeat located in the exon 1 of Huntingtin (HTT) gene in human chromosome 4. The HTT protein is ubiquitously expressed in the brain. Specifically, mutant HTT (mHTT) protein-mediated toxicity leads to a dramatic degeneration of the striatum among many regions of the brain. HD symptoms exhibit a major involuntary movement followed by cognitive and psychiatric dysfunctions. In this review, we address the conventional role of wild type HTT (wtHTT) and how mHTT protein disrupts the function of medium spiny neurons (MSNs). We also discuss how mHTT modulates epigenetic modifications and transcriptional pathways in MSNs. In addition, we define how non-cell autonomous pathways lead to damage and death of MSNs under HD pathological conditions. Lastly, we overview therapeutic approaches for HD. Together, understanding of precise neuropathological mechanisms of HD may improve therapeutic approaches to treat the onset and progression of HD.

SUBMITTER: Kim C

PROVIDER: S-EPMC8617801 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Non-Cell Autonomous and Epigenetic Mechanisms of Huntington's Disease.

Kim Chaebin C Yousefian-Jazi Ali A Choi Seung-Hye SH Chang Inyoung I Lee Junghee J Ryu Hoon H

International journal of molecular sciences 20211119 22

Huntington's disease (HD) is a rare neurodegenerative disorder caused by an expansion of CAG trinucleotide repeat located in the exon 1 of <i>Huntingtin (HTT)</i> gene in human chromosome 4. The HTT protein is ubiquitously expressed in the brain. Specifically, mutant HTT (mHTT) protein-mediated toxicity leads to a dramatic degeneration of the striatum among many regions of the brain. HD symptoms exhibit a major involuntary movement followed by cognitive and psychiatric dysfunctions. In this revi ...[more]

PMID: 34830381

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Dataset Information

Non-Cell Autonomous and Epigenetic Mechanisms of Huntington's Disease.

Publications

Non-Cell Autonomous and Epigenetic Mechanisms of Huntington's Disease.

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