The role of α-synuclein assembly and metabolism in the pathogenesis of Lewy body disease
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Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are members of a family of disorders characterized by the presence of inclusion bodies, or Lewy bodies (LBs), filled with aggregates of α-synuclein. These diseases are a leading cause of movement disorders and dementia in the aging population, and it is crucial to understand the factors leading to the accumulation and assembly of these α-synuclein aggregates. Previous studies have uncovered much about the factors leading to aggregation and the mechanisms causing neurotoxicity of these inclusion bodies; however, little is known about factors that promote the degradation and prevent the aggregation of α-synuclein. The present article provides a review of recent efforts in the investigation of factors involved in α-synuclein metabolism and the mechanisms involved in preventing accumulation of α-synuclein and degrading this molecule. Understanding these processes might provide targets for the development of novel therapies for disorders such as DLB and PD.
Index Entriesα-synuclein degradation metabolism Lewy bodies proteasom ubiquitin
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- Kim J. H., Park K. C., et al. (2003) Deubiquitinating enzymes as cellular regulators. J. Biochem. (Tokyo) 134, 9–18.Google Scholar
- Kim S. J., Sung J. Y., et al. (2003) Parkin cleaves intracellular alpha-synuclein inclusions via the activation of calpain. J. Biol. Chem. 278, 41,890–41,899.Google Scholar
- Osterova-Golts N., Petrucelli L., et al. (2000) The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity. J. Neurosci. 20, 6048–6054.Google Scholar
- Snyder H., Mensah K., et al. (2003) Aggregated and monomeric alpha-synuclein bind to the S6′ proteasomal protein and inhibit proteasomal function. J. Biol. Chem. 278, 11,753–11,759.Google Scholar
- Ueda K., Masliah E., et al. (1993) Novel amyloid component (NAC) differentiates Alzheimer’s disease from normal aging plaques. Soc. Neurosci. Abstr. 19, 1254.Google Scholar
- Zhang Y., Gao J., et al. (2000) Parkin functions as an E2-dependent ubiquitin-protein ligase and promotes the degradation of the synaptic vesicle-associated protein, CDCrel-1. Proc. Natl. Acad. Sci. U.S.A. 97, 13,354–13,359.Google Scholar