Open AccessThe Role of Mitochondria in the Pathogenesis of Neurodegenerative Diseases
Author(s) -
Manfredim Giovanni,
Beal M. Flint
Publication year - 2000
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2000.tb00278.x
Subject(s) - mitochondrion , mitochondrial dna , pathogenesis , biology , epiphenomenon , neurodegeneration , oxidative phosphorylation , dnaja3 , mitochondrial respiratory chain , mitochondrial fusion , programmed cell death , respiratory chain , frataxin , microbiology and biotechnology , genetics , aconitase , medicine , gene , pathology , apoptosis , immunology , biochemistry , disease , philosophy , epistemology
A growing body of evidence indicates that mitochondrial dysfunction may play an important role in the pathogenesis of many neurodegenerative disorders. Because mitochondrial metabolism is not only the principal source of high energy intermediates, but also of free radicals, it has been suggested that inherited or acquired mitochondrial defects could be the cause of neuronal degeneration as a consequence of energy defects and oxidative damage. Mitochondrial respiratory chain dysfunction has been reported in association with primary mitochondrial DNA abnormalities, and also as a consequence of mutations in nuclear genes directly involved in mitochondrial functions, such as SURF1, frataxin, and paraplegin. Defects of oxidative phosphorylation and increased free radical production have also been observed in diseases that are not due to primary mitochondrial abnormalities. In these cases, the mitochondrial dysfunction is likely to be an epiphenomenon, which, nevertheless, could be of importance in precipitating a cascade of events leading to cell death. In either case, understanding the role of mitochondria in the pathogenesis of neurodegenerative diseases could be important for the development of therapeutic strategies in these disorders.