A model of nitric oxide induced α-synuclein misfolding in Parkinson's disease.
Neurosci Lett
; 523(2): 167-73, 2012 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-22776646
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Alfa-Sinucleína
/
Óxido Nítrico
Limite:
Humans
Idioma:
En
Revista:
Neurosci Lett
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos