Protein Aggregation and Pathogenesis of Huntingtons Disease: Mechanisms and Correlations
- 13 September 2000
- journal article
- review article
- Published by Walter de Gruyter GmbH in Biological Chemistry
- Vol. 381 (9-10), 937-942
- https://doi.org/10.1515/bc.2000.114
Abstract
The formation of insoluble protein aggregates is a hallmark of Huntington's disease (HD) and related neurodegenerative disorders, such as dentatorubral pallidoluysian atrophy (DRPLA), spinal bulbar muscular atrophy (SBMA) and the spinocerebellar ataxia (SCA) type 1, 2, 3, 6 and 7. These disorders are caused by an expanded polyglutamine (polyQ) tract in otherwise unrelated proteins. They are characterized by late-onset, selective neuropathology, a pathogenic polyQ threshold and a relationship between polyQ length and disease progression. Thus, molecular models of HD and related glutamine-repeat disorders must account for these characteristic features. During the last three years, considerable effort has been invested in the development of in vitro and in vivo model systems to study the mechanisms of protein aggregation in glutamine-repeat disorders and its potential effects on disease progression and neurodegeneration. A selection of these studies is reviewed here. Furthermore, the correlation between aggregate formation and development of HD is discussed.Keywords
This publication has 42 references indexed in Scilit:
- Inhibition of huntingtin fibrillogenesis by specific antibodies and small molecules: Implications for Huntington's disease therapyProceedings of the National Academy of Sciences, 2000
- Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretchNature Genetics, 1998
- Aggregation of Huntingtin in Neuronal Intranuclear Inclusions and Dystrophic Neurites in BrainScience, 1997
- Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tractNature Genetics, 1996
- Expanded polyglutamine in the Machado–Joseph disease protein induces cell death in vitro and in vivoNature Genetics, 1996
- Absence of Disease Phenotype and Intergenerational Stability of the Cag Repeat in Transgenic Mice Expressing the Human Huntington Disease TranscriptHuman Molecular Genetics, 1996
- SCA1 transgenic mice: A model for neurodegeneration caused by an expanded CAG trinucleotide repeatCell, 1995
- Huntington’s Disease: Recent Advances in Diagnosis and ManagementCanadian Journal of Neurological Sciences, 1995
- Human genetic diseases due to codon reiteration: Relationship to an evolutionary mechanismCell, 1993
- A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomesCell, 1993