Energetics and oxidative stress in synaptic plasticity and neurodegenerative disorders

Mark P. Mattson, Dong Liu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)215-231
Number of pages17
JournalNeuroMolecular Medicine
Volume2
Issue number2
DOIs
StatePublished - 2002

Keywords

  • Alzheimer's
  • ATP
  • Calcium
  • Hippocampus
  • Mitochondria
  • Neurotrophic
  • Parkinson
  • Superoxide

ASJC Scopus subject areas

  • Neuroscience(all)
  • Genetics
  • Cell Biology

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