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PMID: 12428812 Published · ppublish English Journal Article Review

Energetics and oxidative stress in synaptic plasticity and neurodegenerative disorders.

Neuromolecular medicine ·Vol. 2 ·No. 2 ·2002-00-00 ·Pages 215-31

Mattson MP, Liu D

Abstract

As in other cells, neurons use adenosine triphosphate (ATP) as an energy source to drive biochemical processes involved in various cell functions, and produce reactive oxygen species (ROS) as "by products" of oxidative phosphorylation. However, the electrical excitability and structural and synaptic complexity of neurons present unusual demands upon cellular systems that produce or respond to ATP and ROS. Mitochondria in axons and presynaptic terminals provide sources of ATP to drive the ion pumps that are concentrated in these structures to rapidly restore ion gradients following depolarization and neurotransmitter release. Mitochondria may also play important roles in the regulation of synaptic function because of their ability to regulate calcium levels and ROS production. ROS generated in response to synaptic activity are now known to contribute to the regulation of long-term structural and functional changes in neurons, and the best-known example is the nitric oxide radical. The high-energy demands of synapses, together with their high levels of ROS production, place them at risk during conditions of increased stress, which occur in aging, neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, and after acute traumatic and ischemic insults. Energy depletion and/or increased oxidative damage to various synaptic proteins can result in a local dysregulation of calcium homeostasis and synaptic degeneration. Accordingly, recent studies have shown that dietary and pharmacological manipulations that improve energy efficiency and reduce oxyradical production can prevent synaptic degeneration and neuronal death in experimental models of neurodegenerative disorders. A better understanding of the molecular control of subcellular energy production and utilization, and of the functional relationships between energy metabolism, ion homeostasis, and cytoskeletal and vesicular dynamics, will provide novel insight into mechanisms of neuronal plasticity and disease.

MeSH Terms
Adenosine Triphosphate/metabolism Animals Energy Metabolism/physiology Humans Mitochondria/metabolism Neurodegenerative Diseases/metabolism,pathology,physiopathology Neuronal Plasticity/physiology Oxidative Stress/physiology Reactive Oxygen Species/metabolism Synapses/metabolism Synaptic Transmission/physiology
Chemicals
Reactive Oxygen Species Adenosine Triphosphate
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Mattson Mark P
Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center, Baltimore, MD 21224, USA. [email protected]
Liu Dong
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Article Info
Journal
Neuromolecular medicine
Abbr.
Neuromolecular Med
ISSN
1535-1084
DOI
10.1385/NMM:2:2:215
Email
[email protected]
Published
2002-00-00
Pages
215-31
Language
English
Region
United States
NLM ID
101135365
Subset
IM
External Links
PubMed source DOI: 10.1385/NMM:2:2:215 View journal details
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