Kim, C. Yousefian-Jazi, A. Choi, S.-H. Chang, I. Lee, J. Ryu, H. 2024-01-19T13:31:45Z 2024-01-19T13:31:45Z 2022-01-10 2021-11 1661-6596 https://pubs.kist.re.kr/handle/201004/116196 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) pro-tein-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. ？ 2021 by the authors. Licensee MDPI, Basel, Switzerland. English Multidisciplinary Digital Publishing Institute (MDPI) Non-cell autonomous and epigenetic mechanisms of huntington’s disease Article 10.3390/ijms222212499 1 International Journal of Molecular Sciences, v.22, no.22 International Journal of Molecular Sciences 22 22 Y scie scopus 000726013100001 2-s2.0-85119253451 Biochemistry & Molecular Biology Chemistry, Multidisciplinary Biochemistry & Molecular Biology Chemistry Review TRANSGENIC MOUSE MODEL POLYGLUTAMINE-EXPANDED HUNTINGTIN MEDIUM SPINY NEURONS MUTANT HUNTINGTIN DNA METHYLATION IN-VIVO AXONAL-TRANSPORT GENE-EXPRESSION MESSENGER-RNA MITOCHONDRIAL DYSFUNCTION Astrocyte Epigenetics Huntington’s disease Mitochondria dysfunction Non-cell autonomous pathway Oligodendrocyte Therapeutic targets Vesicle trafficking