title: 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.
authors.affiliation: Department of Biochemistry and Nutrition, Central Food Technological Research Institute (CSIR unit), Mysore-570020, India.
authors.forename: Muralidhar L
authors.initials: ML
authors.lastname: Hegde
authors.forename: Padmaraju
authors.initials: P
authors.lastname: Vasudevaraju
authors.forename: Kosagisharaf Jagannatha
authors.initials: KJ
authors.lastname: Rao
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009690:Nucleic Acid Conformation; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D017510:Protein Folding; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein; D004247:DNA