title: Recent advances in α-synuclein functions, advanced glycation, and toxicity: implications for Parkinson's disease.
abstract: The toxicity of α-synuclein in the neuropathology of Parkinson's disease which includes its hallmark aggregation has been studied scrupulously in the last decade. Although little is known regarding the normal functions of α-synuclein, its association with membrane phospholipids suggests its potential role in signaling pathways. Following extensive evidences for its nuclear localization, we and others recently demonstrated DNA binding activity of α-synuclein that modulates its conformation as well as aggregation properties. Furthermore, we also underscored the similarities among various amyloidogenic proteins involved in neurodegenerative diseases including amyloid beta peptides and tau. Our more recent studies show that α-synuclein is glycated and glycosylated both in vitro and in neurons, significantly affecting its folding, oligomeric, and DNA binding properties. Glycated α-synuclein causes increased genome damage both via its direct interaction with DNA and by increased generation of reactive oxygen species as glycation byproduct. In this review, we discuss the mechanisms of glycation and other posttranslational modifications of α-synuclein, including phosphorylation and nitration, and their role in neuronal death in Parkinson's disease.
authors.affiliation: Centre for Neuroscience, Institute for Scientific Research and Technological Services (INDICASAT-AIP), City of Knowledge, Panama, Republic of Panama.
authors.forename: Erika
authors.initials: E
authors.lastname: Guerrero
authors.forename: P
authors.initials: P
authors.lastname: Vasudevaraju
authors.forename: Muralidhar L
authors.initials: ML
authors.lastname: Hegde
authors.forename: G B
authors.initials: GB
authors.lastname: Britton
authors.forename: K S
authors.initials: KS
authors.lastname: Rao
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D017510:Protein Folding; D051844:alpha-Synuclein / Q000009:adverse effects / Q000502:physiology* / Q000633:toxicity
chemical_list: D017127:Glycation End Products, Advanced; D051844:alpha-Synuclein