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Sci. Signal., 5 May 2009
Vol. 2, Issue 69, p. pe29
Nitric Oxide Links Mitochondrial Fission to Alzheimers Disease
Institut für Zellbiologie and Bayreuther Zentrum für Molekulare Biowissenschaften, Universität Bayreuth, 95440 Bayreuth, Germany.
Mitochondrial dysfunction is a hallmark of β-amyloid (Aβ)–induced neuronal injury in the pathogenesis of Alzheimers disease. Neurotoxic Aβ peptide, thought to be a key mediator of Alzheimers disease, may be imported into human brain mitochondria, where it inhibits key enzymes of respiratory metabolism. Nitric oxide (NO) produced in response to Aβ 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 Alzheimers disease contain high amounts of S-nitrosylated Drp-1. Aβ-dependent mitochondrial fragmentation likely enhances the decline in bioenergetic capacity of damaged mitochondria and therefore contributes to neuronal injury and pathogenesis of Alzheimers disease.