Mitochondria, oxidative stress and neurodegeneration.
Mitochondria are involved in ATP supply to cells through oxidative phosphorylation (OXPHOS), synthesis of key molecules and response to oxidative stress, as well as in apoptosis. They contain many redox enzymes and naturally occurring inefficiencies of oxidative phosphorylation generate reactive oxygen species (ROS). CNS functions depend heavily on efficient mitochondrial function, since brain tissue has a high energy demand. Mutations in mitochondrial DNA (mtDNA), generation and presence of ROS and environmental factors may contribute to energy failure and lead to neurodegenerative diseases. Many rare metabolic disorders have been associated with mitochondrial dysfunction. More than 300 pathogenic mtDNA mutations involve proteins that regulate OXPHOS and mitochondrial structural integrity, and have also been described in neurodegenerative diseases with autosomal inheritance. Mitochondria may have an important role in ageing-related neurodegenerative disorders like Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). In primary mitochondrial and neurodegenerative disorders, there is strong evidence that mitochondrial dysfunction occurs early and has a primary role in pathogenesis. In the present review, we discuss several mitochondrial diseases as models of neurodegeneration.
Department of Neurological, Neurosurgical and Behavioural Sciences, Medical School, University of Siena, Italy. federico@unisi.it
Antonio
A
Federico
Elena
E
Cardaioli
Paola
P
Da Pozzo
Patrizia
P
Formichi
Gian Nicola
GN
Gallus
Elena
E
Radi
D000375:Aging; D017209:Apoptosis; D001921:Brain / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics; D006801:Humans; D028361:Mitochondrial Diseases / Q000209:etiology* / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000150:complications* / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species