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A model of nitric oxide induced ?-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 (?-syn). Moreover, nitration of ?-syn promotes protein aggregation in disease. To model such pathological events, we constructed controllable iNOS and bicistronic ?-syn-IRES-tTA adeno-associated virus (AAV) expression vectors. Transduction of iNOS and ?-syn AAV constructs led to nitration of ?-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.

SUBMITTER: Stone DK

PROVIDER: S-EPMC3408780 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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A model of nitric oxide induced α-synuclein misfolding in Parkinson's disease.

Stone David K DK Kiyota Tomomi T Mosley R Lee RL Gendelman Howard E HE

Neuroscience letters 20120707 2

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 eve ...[more]

PMID: 22776646

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