Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease

Abstract

Alzheimer disease (AD) and Parkinson disease (PD) are the two most common age-related neurodegenerative diseases characterized by prominent neurodegeneration in selective neural systems. Although a small fraction of AD and PD cases exhibit evidence of heritability, among which many genes have been identified, the majority are sporadic without known causes. Molecular mechanisms underlying neurodegeneration and pathogenesis of these diseases remain elusive. Convincing evidence demonstrates oxidative stress as a prominent feature in AD and PD and links oxidative stress to the development of neuronal death and neural dysfunction, which suggests a key pathogenic role for oxidative stress in both AD and PD. Notably, mitochondrial dysfunction is also a prominent feature in these diseases, which is likely to be of critical importance in the genesis and amplification of reactive oxygen species and the pathophysiology of these diseases. In this review, we focus on changes in mitochondrial DNA and mitochondrial dynamics, two aspects critical to the maintenance of mitochondrial homeostasis and function, in relationship with oxidative stress in the pathogenesis of AD and PD.

Keywords: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyradine; AD; ADDL; APP; Alzheimer disease; ApoE4; Aβ; Aβ-derived diffusible ligand; COX; DLP1, aka Drp1; ETC; Free radicals; LHON; LRRK2 or PARK8; Leber's hereditary optic neuropathy; MERRF; MMP; MPTP; Mfn; Mitochondrial DNA; Mitochondrial dynamics; Mitochondrial dysfunction; OMM; OPA-1; OXPHOS; Oxidative stress; PD; PINK1 or PARK6; PS; PTEN-induced putative kinase; Parkinson disease; ROS; SNP; SOD; amyloid-β; amyloid-β protein precursor; apolipoprotein E; cytochrome c oxidase; dynamin-like protein 1; electron transport chain; leucine-rich repeat kinase 2; mitochondrial DNA; mitochondrial membrane potential; mitofusin; mtDNA; myoclonic epilepsy with red ragged fibers syndrome; optic atrophy protein 1; outer mitochondrial membrane; oxidative phosphorylation; presenilin; reactive oxygen species; single-nucleotide polymorphism; superoxide dismutase.