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

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

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)167-173
Number of pages7
JournalNeuroscience Letters
Volume523
Issue number2
DOIs
StatePublished - Aug 15 2012

Fingerprint

Synucleins
Nitric Oxide Synthase Type II
Dependovirus
Parkinson Disease
Nitric Oxide
Proteins
alpha-Synuclein
Cell Death
Up-Regulation
Neurons
Wounds and Injuries

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A model of nitric oxide induced α-synuclein misfolding in Parkinson's disease. / Stone, David K.; Kiyota, Tomomi; Mosley, R Lee; Gendelman, Howard Eliot.

In: Neuroscience Letters, Vol. 523, No. 2, 15.08.2012, p. 167-173.

Research output: Contribution to journalArticle

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