Dopamine and L-dopa disaggregate amyloid fibrils: implications for Parkinson's and Alzheimer's disease

SPECIFIC AIMSOur aims were to 1) show that catecholamines such as dopamine and L-dopa inhibit formation of amyloid fibrils by Aβ and α-synuclein, and disaggregate existing fibrils of Aβ or α-synuclein, and 2) determine mechanisms of catecholamine inhibition of fibrillation and fibril disaggregation.PRINCIPAL FINDINGS1. Catecholamines (dopamine, L-dopa, epinephrine) inhibit fibrillation of Aβ and α-synucleinUsing a thioflavin T assay, light scattering, EM, and AFM, we show that micromolar concentrations of dopamine, L-dopa, norepinephrine, and epinephrine inhibit in vitro formation of amyloid fibrils of Aβ and α-synuclein. Amount of inhibition was dependent on concentration of dopamine or L-dopa. For α-synuclein, size exclusion chromatography demonstrated that the major product of inhibition of α-synuclein is oligomeric and involves covalent modification of the protein. CD and FTIR experiments showed that changes in conformation of soluble α-synuclein during fibrillation (increased β-structure) were absent...