Mechanisms of alpha-Synuclein Aggregation and Toxicity
Abstract
ALPHA-Synuclein is a protein that aggregates to form pathological structures, termed Lewy bodies, in the brains of patients with Parkinson's disease (PD). Aggregation of alpha- synuclein is thought to be harmful to neurons, and mutations that increase the tendency of alpha-synuclein to aggregate are associated with familial PD. The aim of this proposal is to understand factors that stimulate or inhibit alpha-synuclein aggregation, and the methods focus on metals, which our preliminary data suggests modulates alpha-synuclein aggregation. During the first year of this proposal we characterized the affects of eight metal ions on alpha-synuclein aggregation in vitro: iron (II and III), copper (II), Nickel (II), Manganese (II), Magnesium (II), Zinc (II), Calcium (II, not a metal, but tested) and Aluminum (III). We observed three classes of interaction based on conformational changes and aggregation. Iron and copper induced alpha-synuclein aggregation. Magnesium, Calcium and Zinc caused similar conformational changes; magnesium inhibited alpha-synuclein aggregation, zinc caused dimerization and calcium caused only conformational changes. The other metals had no effect. Iron (II), Copper and Magnesium exerted similar effects in neurons grown in cell culture, suggesting that magnesium might be useful in preventing the pathology of PD.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA419539
Entities
People
- Benjamin Wolozin
Organizations
- Loyola University New Orleans