ABSTRACT
Regulation of mitochondrial homeostasis inuences the progression of neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and prion diseases (Dragicevic et al. 2011; Jeong et al. 2012; Olcese et al. 2009; Paradies et al. 2010; Quintanilla et al. 2011; Singhal et al. 2011). In vivo experiments have shown that melatonin administration restores mitochondrial function by enhancing mitochondrial glutathione levels and ATP synthesis by stimulating NADH-coenzyme Q reductase (complex I) and cytochrome c oxidase (complex IV) activities in a transgenic mice model of Alzheimer’s disease (Dabbeni-Sala et al. 2001). Melatonin also exerts a protective effect against the 1-methyl-4-phenylpyridine (MPP+)-induced neuronal cell death and mitochondrial dysfunction by the inhibition of p38 mitogen-activated protein kinase, p53, and GSK-3β phosphorylation (Absi et al. 2000). In addition, melatonin protects amyloid-beta peptide 25-to 35-induced mitochondrial dysfunction in hippocampal neurons (Dong et al. 2010). And also, it may protect against anesthesiainduced apoptotic neurodegeneration via improved mitochondrial homeostasis (Yon et al. 2006). In addition, a recent study suggested that melatonin administration protects from glutamate-induced oxytosis by an antioxidant effect that specically targets mitochondria (Herrera et al. 2007). And also the typical pattern of neurotoxicity in prion disease is through mitochondrial damage.
