Journal
FASEB JOURNAL
Volume 18, Issue 6, Pages 962-+Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.03-0770fje
Keywords
alpha-synuclein; A beta peptide; catecholamines; oxidation
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Funding
- NIEHS NIH HHS [R01 ES10806] Funding Source: Medline
- NINDS NIH HHS [R01 NS39985] Funding Source: Medline
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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.
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