Polyglutamine pathogenesis: emergence of unifying mechanisms for Huntington's disease and related disorders
- PMID: 12372277
- DOI: 10.1016/s0896-6273(02)00872-3
Polyglutamine pathogenesis: emergence of unifying mechanisms for Huntington's disease and related disorders
Abstract
The mechanisms of neurodegeneration in the CAG repeat polyglutamine diseases, including Spinal and Bulbar Muscular Atrophy (SBMA), Huntington's disease (HD), DentatoRubral and PallidoLuysian Atrophy (DRPLA), and Spino-Cerebellar Ataxia (SCA), have been controversial. Issues have included the role of polyglutamine aggregation and possible amyloid formation, localization in the cell nucleus, and possible proteolytic processing. Proposed mechanisms have included activation of caspases or other triggers of apoptosis, mitochondrial or metabolic toxicity, and interference with gene transcription. Recent studies using transgenic mouse and Drosophila models have helped resolve some of these issues and raise hopes for development of therapeutic targets.
Similar articles
-
Polyglutamine (PolyQ) Diseases: Navigating the Landscape of Neurodegeneration.ACS Chem Neurosci. 2024 Aug 7;15(15):2665-2694. doi: 10.1021/acschemneuro.4c00184. Epub 2024 Jul 12. ACS Chem Neurosci. 2024. PMID: 38996083 Free PMC article. Review.
-
[Molecular biology of polyglutamine diseases].Postepy Hig Med Dosw. 2002;56(6):779-88. Postepy Hig Med Dosw. 2002. PMID: 12661407 Review. Polish.
-
[The Role of Mutant RNA in the Pathogenesis of Huntington's Disease and Other Polyglutamine Diseases].Mol Biol (Mosk). 2019 Nov-Dec;53(6):954-967. doi: 10.1134/S002689841906003X. Mol Biol (Mosk). 2019. PMID: 31876275 Review. Russian.
-
Protein aggregation and pathogenesis of Huntington's disease: mechanisms and correlations.Biol Chem. 2000 Sep-Oct;381(9-10):937-42. doi: 10.1515/BC.2000.114. Biol Chem. 2000. PMID: 11076024 Review.
-
The CAG-polyglutamine repeat diseases: a clinical, molecular, genetic, and pathophysiologic nosology.Handb Clin Neurol. 2018;147:143-170. doi: 10.1016/B978-0-444-63233-3.00011-7. Handb Clin Neurol. 2018. PMID: 29325609 Review.
Cited by
-
Identification of molecular signatures defines the differential proteostasis response in induced spinal and cranial motor neurons.Cell Rep. 2024 Mar 26;43(3):113885. doi: 10.1016/j.celrep.2024.113885. Epub 2024 Mar 7. Cell Rep. 2024. PMID: 38457337 Free PMC article.
-
Modification of Huntington's disease by short tandem repeats.Brain Commun. 2024 Jan 23;6(2):fcae016. doi: 10.1093/braincomms/fcae016. eCollection 2024. Brain Commun. 2024. PMID: 38449714 Free PMC article.
-
HD and SCA1: Tales from two 30-year journeys since gene discovery.Neuron. 2023 Nov 15;111(22):3517-3530. doi: 10.1016/j.neuron.2023.09.036. Epub 2023 Oct 19. Neuron. 2023. PMID: 37863037 Review.
-
Possible Role of Mitochondrial Transfer RNA Gene 5816 A > G Genetic Polymorphism (m.5816A > G) in a 3-Year-Old Child with Dystonia: Report of a Case.Glob Med Genet. 2023 Sep 27;10(3):263-270. doi: 10.1055/s-0043-1774708. eCollection 2023 Sep. Glob Med Genet. 2023. PMID: 37771542 Free PMC article.
-
Proteotoxic stresses stimulate dissociation of UBL4A from the tail-anchored protein recognition complex.Biochem J. 2023 Oct 11;480(19):1583-1598. doi: 10.1042/BCJ20230267. Biochem J. 2023. PMID: 37747814 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases