title: A model of nitric oxide induced α-synuclein misfolding in Parkinson's disease.
abstract: Inducible nitric oxide synthase (iNOS) upregulation and consequent NO formation are well-recognized neuroinflammatory responses associated with Parkinson's disease (PD). These contribute to nitrosative protein modifications affecting neuronal injury and cell death. Indeed, a pathobiologic signature for PD is Lewy body formation containing misfolded and aggregated forms of alpha-synuclein (α-syn). Moreover, nitration of α-syn promotes protein aggregation in disease. To model such pathological events, we constructed controllable iNOS and bicistronic α-syn-IRES-tTA adeno-associated virus (AAV) expression vectors. Transduction of iNOS and α-syn AAV constructs led to nitration of α-syn in neurons and overexpression of iNOS promoted protein aggregation. We posit that this AAV system mimics critical protein misfolding events associated with the pathogenesis of PD.
authors: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors: David K
authors: DK
authors: Stone
authors: Tomomi
authors: T
authors: Kiyota
authors: R Lee
authors: RL
authors: Mosley
authors: Howard E
authors: HE
authors: Gendelman
mesh_terms: D000229:Dependovirus / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D017510:Protein Folding; D014161:Transduction, Genetic; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II