PMC:3023298 / 6375-7925
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3023298","sourcedb":"PMC","sourceid":"3023298","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3023298","text":"Mitochondrial perturbations are known to participate in the mechanisms of human neuropathology, particularly disorders involving acute interruptions in O2 and substrate delivery to the brain and bioenergetic failure as seen in tissue ischemia and toxic exposures [6]. Optic atrophy type 1 (OPA1), a hereditary optic neuropathy, is one example of a chronic neurodegenerative disease caused by mutations in the OPA1 gene that encodes a mitochondrial dynamin-related GTPase that functions in maintenance of mitochondrial morphology, including fusion, and metabolism [16]. The properties and functions of mitochondria (Figure 1) might confer an intrinsic susceptibility of subsets of long-lived post-mitotic cells such as neurons to aging and stresses, including mutations and environmental toxins. This review summarizes the contributions of the different forms of cell death to three human neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis), the evidence for mitochondrial involvement, and their animal and cell models. In this regard varying degrees of mitochondrial dysfunction and intrinsic mitochondrial-mediated cell death mechanisms could be critical determinants in the regulation of disease and neuronal cell death ranging from necrosis and apoptosis to autophagy [17,18,19]; thus, targeting mitochondrial properties or entities, such as the mitochondrial PTP (Figure 1) [20,21,22,23], could be important for developing new mechanism-based pharmaco-therapies for neurodegenerative 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