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- Title
Mitochondria, a Key Target in Amyotrophic Lateral Sclerosis Pathogenesis.
- Authors
Genin, Emmanuelle C.; Abou-Ali, Mélanie; Paquis-Flucklinger, Véronique
- Abstract
Mitochondrial dysfunction occurs in numerous neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS), where it contributes to motor neuron (MN) death. Of all the factors involved in ALS, mitochondria have been considered as a major player, as secondary mitochondrial dysfunction has been found in various models and patients. Abnormal mitochondrial morphology, defects in mitochondrial dynamics, altered activities of respiratory chain enzymes and increased production of reactive oxygen species have been described. Moreover, the identification of CHCHD10 variants in ALS patients was the first genetic evidence that a mitochondrial defect may be a primary cause of MN damage and directly links mitochondrial dysfunction to the pathogenesis of ALS. In this review, we focus on the role of mitochondria in ALS and highlight the pathogenic variants of ALS genes associated with impaired mitochondrial functions. The multiple pathways demonstrated in ALS pathogenesis suggest that all converge to a common endpoint leading to MN loss. This may explain the disappointing results obtained with treatments targeting a single pathological process. Fighting against mitochondrial dysfunction appears to be a promising avenue for developing combined therapies in the future.
- Subjects
AMYOTROPHIC lateral sclerosis; MITOCHONDRIA; CYTOCHROME oxidase; REACTIVE oxygen species; MOTOR neurons; MOTOR neuron diseases
- Publication
Genes, 2023, Vol 14, Issue 11, p1981
- ISSN
2073-4425
- Publication type
Article
- DOI
10.3390/genes14111981