Dopamine and L‐dopa disaggregate amyloid fibrils: implications for Parkinson's and Alzheimer's disease
- 14 April 2004
- journal article
- fj express-summary
- Published by Wiley in The FASEB Journal
- Vol. 18 (9), 962-964
- https://doi.org/10.1096/fj.03-0770fje
Abstract
Protein deposition diseases involve the aggregation of normally soluble proteins, leading to both fibrillar and amorphous deposits. The aggregation of alpha-synuclein is associated with Parkinson's disease, and the aggregation of the Abeta peptide is associated with Alzheimer's disease. Here we show that L-dopa, dopamine, and other catecholamines dissolve fibrils of alpha-synuclein and Abeta peptide generated in vitro. The catecholamines also inhibited the fibrillation of these proteins. In addition, intraneuronal alpha-synuclein deposits formed in a mouse model were dissolved by incubation of tissue slices with L-dopa. These catecholamines are susceptible to oxidative breakdown, and we show that oxidation products are more effective than the parent compounds in inhibition. The ability to dissolve fibrils provides a new approach for studying mechanisms and consequences (e.g., the relationship between fibril formation and neurodegeneration) of protein aggregation. It is also likely to help in the development of strategies for the prevention and treatment of protein deposition diseases.Keywords
Funding Information
- National Institutes of Health (RO1 NS39985, RO1 ES10806)
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