Nitric oxide links mitochondrial fission to Alzheimer's disease.
Mitochondrial dysfunction is a hallmark of beta-amyloid (Abeta)-induced neuronal injury in the pathogenesis of Alzheimer's disease. Neurotoxic Abeta peptide, thought to be a key mediator of Alzheimer's disease, may be imported into human brain mitochondria, where it inhibits key enzymes of respiratory metabolism. Nitric oxide (NO) produced in response to Abeta induces S-nitrosylation of the mitochondrial division protein, dynamin-related protein 1 (Drp-1), which leads to excessive mitochondrial fission, synaptic loss, and neuronal damage. Furthermore, brains of patients with Alzheimer's disease contain high amounts of S-nitrosylated Drp-1. Abeta-dependent mitochondrial fragmentation likely enhances the decline in bioenergetic capacity of damaged mitochondria and therefore contributes to neuronal injury and pathogenesis of Alzheimer's disease.
Institut für Zellbiologie and Bayreuther Zentrum für Molekulare Biowissenschaften, Universität Bayreuth, 95440 Bayreuth, Germany. benedikt.westermann@uni-bayreuth.de
Benedikt
B
Westermann
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D024101:Mitochondrial Proteins / Q000378:metabolism; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D009569:Nitric Oxide; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins