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- Title
Impaired mitochondrial homeostasis and neurodegeneration: towards new therapeutic targets?
- Authors
Corona, Juan; Duchen, Michael
- Abstract
The sustained integrity of the mitochondrial population of a cell is critical for maintained cell health, and disruption of that integrity is linked strongly to human disease, especially to the neurodegenerative diseases. These are appalling diseases causing untold levels of suffering for which treatment is woefully inadequate. Understanding the mechanisms that disturb mitochondrial homeostasis may therefore prove key to identification of potential new therapeutic pathways. Mechanisms causing mitochondrial dysfunction include the acute catastrophic loss of function caused by opening of the mitochondrial permeability transition pore (mPTP), which collapses bioenergetic function and initiates cell death. This is best characterised in ischaemic reperfusion injury, although it may also contribute to a number of other diseases. More insidious disturbances of mitochondrial homeostasis may result from impaired balance in the pathways that promote mitochondrial repair (biogenesis) and pathways that remove dysfunctional mitochondria (mitophagy). Impaired coordination between these processes is emerging as a key feature of a number of neurodegenerative and neuromuscular disorders. Here we review pathways that may prove to be valuable potential therapeutic targets, focussing on the molecular mechanisms that govern the coordination of these processes and their involvement in neurodegenerative diseases.
- Subjects
MITOCHONDRIA; HOMEOSTASIS; TREATMENT of neurodegeneration; DRUG development; REPERFUSION injury
- Publication
Journal of Bioenergetics & Biomembranes, 2015, Vol 47, Issue 1/2, p89
- ISSN
0145-479X
- Publication type
Article
- DOI
10.1007/s10863-014-9576-6