title: The Cytomegalovirus protein pUL37×1 targets mitochondria to mediate neuroprotection.
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.
authors: Department of Clinical Neuroscience, UCL Institute of Neurology, University College London, UK.|Department of Neurology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.|Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors: Chien Tai
authors: CT
authors: Hong
authors: Department of Clinical Neuroscience, UCL Institute of Neurology, University College London, UK.
authors: Kai-Yin
authors: KY
authors: Chau
authors: Department of Clinical Neuroscience, UCL Institute of Neurology, University College London, UK.
authors: Anthony H V
authors: AH
authors: Schapira
mesh_terms: D000818:Animals; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D006019:Glycolysis; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D063306:Mitophagy / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine / Q000009:adverse effects; D021381:Protein Transport; D051381:Rats; D019311:Staurosporine / Q000009:adverse effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; D017874:Immediate-Early Proteins; D018696:Neuroprotective Agents; C420323:UL37 protein, Human herpesvirus 5; D051028:bcl-2-Associated X Protein; D016627:Oxidopamine; D019311:Staurosporine