DNA induced folding/fibrillation of alpha-synuclein: new insights in Parkinson's disease

Front Biosci (Landmark Ed). 2010 Jan 1;15:418-36. doi: 10.2741/3628.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism*
  • Humans
  • Models, Biological
  • Nucleic Acid Conformation
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • Parkinson Disease / pathology
  • Protein Binding
  • Protein Folding
  • alpha-Synuclein / chemistry
  • alpha-Synuclein / metabolism*

Substances

  • alpha-Synuclein
  • DNA