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

David K. Stone, Tomomi Kiyota, R. Lee Mosley, Howard E. Gendelman

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)167-173
Number of pages7
JournalNeuroscience Letters
Issue number2
StatePublished - Aug 15 2012


  • Adeno-associated virus
  • Alpha-synuclein
  • Atomic force microscopy
  • Nitration
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)


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