The Cytomegalovirus protein pUL37×1 targets mitochondria to mediate neuroprotection.
Sci Rep
; 6: 31373, 2016 08 26.
Article
em En
| MEDLINE
| ID: mdl-27562039
ABSTRACT
There is substantial evidence that mitochondrial dysfunction plays a significant role in the pathogenesis of Parkinson disease (PD). This contribution probably encompasses defects of oxidative phosphorylation, mitochondrial turnover (mitophagy), mitochondrial derived oxidative stress, and apoptotic signalling. Human cytomegalovirus immediate-early protein pUL37 × 1 induces Bax mitochondrial translocation and inactivation to prevent apoptosis. Over-expressing pUL37 × 1 in neuronal cells protects against staurosporin and 6-hydroxydopamine induced apoptosis and cell death. Protection is not enhanced by bax silencing in pUL37 × 1 over-expressing cells, suggesting a bax-dependent mechanism of action. pUL37 × 1 increases glycolysis and induces mitochondrial hyperpolarization, a bax independent anti-apoptotic action. pUL37 × 1 increases glycolysis through activation of phosphofructokinase by a calcium-dependent pathway. The dual anti-apoptotic mechanism of pUL37 × 1 may be considered a novel neuroprotective strategy in diseases where mitochondrial dysfunction and apoptotic pathways are involved.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Imediatamente Precoces
/
Fármacos Neuroprotetores
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Citomegalovirus
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Proteína X Associada a bcl-2
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Mitocôndrias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Reino Unido