DNA induced folding/fibrillation of alpha-synuclein: new insights in Parkinson's disease
- PMID: 20036828
- DOI: 10.2741/3628
DNA induced folding/fibrillation of alpha-synuclein: new insights in Parkinson's disease
Abstract
Emerging evidences on the nuclear localization of alpha-Synuclein in neurons and a close look in to its primary sequence/structural organization led us to examine its DNA binding ability. Subsequently, we first time demonstrated the interaction of DNA with alpha-Synuclein which was also confirmed by others. We recently showed that double-stranded oligos induce partial folding in alpha-Synuclein and promote its aggregation, where as single-strand circular DNA and supercoiled plasmid DNA induced a helix-rich conformation and protected the protein from fibrillation. In turn, alpha-Synuclein modulates DNA conformation from B- to an altered B-form, which may affect DNA transactions. Interestingly, amyloid-beta peptides and prion proteins implicated in Alzheimer's disease and Prion diseases respectively, were also shown to have DNA binding activity which suggests that DNA binding may be a common property of many amyloidogenic proteins associated with various neurodegenerative disorders. In this review, we debate the biological significance of DNA-alpha-Synuclein interactions; it's beneficial vs. toxic role in relevance to Parkinson's disease.
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