Journal
PHARMACOLOGICAL RESEARCH
Volume 138, Issue -, Pages 2-15Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2018.08.010
Keywords
Mitochondrial dynamics; P110; Drp1; Neurodegeneration; Neuroinflammation; Protein-Protein interactions
Categories
Funding
- National Institutes of Health [NIAAA11147]
- Mitoconix Bioscience
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Mitochondria are best known for their role in ATP generation. However, studies over the past two decades have shown that mitochondria do much more than that. Mitochondria regulate both necrotic and apoptotic cell death pathways, they store and therefore coordinate cellular Ca2+ signaling, they generate and metabolize important building blocks, by-products and signaling molecules, and they also generate and are targets of free radical species that modulate many aspects of cell physiology and pathology. Most estimates suggest that although the brain makes up only 2 percent of body weight, utilizes about 20 percent of the body's total ATP. Thus, mitochondria! dysfunction greatly impacts brain functions and is indeed associated with numerous neurodegenerative diseases. Furthermore, a number of abnormal disease-associated proteins have been shown to interact directly with mitochondria, leading to mitochondrial dysfunction and subsequent neuronal cell death. Here, we discuss the role of mitochondrial dynamics impairment in the pathological processes associated with neurode-generation and suggest that a therapy targeting mitochondrialdysfunction holds a great promise.
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