Mitochondria, calcium-dependent neuronal death and neurodegenerative disease

Pflugers Arch. 2012 Jul;464(1):111-21. doi: 10.1007/s00424-012-1112-0. Epub 2012 May 22.

Abstract

Understanding the mechanisms of neuronal dysfunction and death represents a major frontier in contemporary medicine, involving the acute cell death in stroke, and the attrition of the major neurodegenerative diseases, including Parkinson's, Alzheimer's, Huntington's and Motoneuron diseases. A growing body of evidence implicates mitochondrial dysfunction as a key step in the pathogenesis of all these diseases, with the promise that mitochondrial processes represent valuable potential therapeutic targets. Each disease is characterised by the loss of a specific vulnerable population of cells--dopaminergic neurons in Parkinson's disease, spinal motoneurons in Motoneuron disease, for example. We discuss the possible roles of cell type-specific calcium signalling mechanisms in defining the pathological phenotype of each of these major diseases and review central mechanisms of calcium-dependent mitochondrial-mediated cell death.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Calcium Signaling*
  • Cell Death
  • Glutamic Acid / metabolism
  • Humans
  • Mitochondria / metabolism*
  • Mitochondrial Membrane Transport Proteins / metabolism
  • Mitochondrial Permeability Transition Pore
  • Neurodegenerative Diseases / etiology*
  • Neurons / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Receptors, Glutamate / metabolism

Substances

  • Calcium Channels
  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Receptors, Glutamate
  • Glutamic Acid
  • Poly(ADP-ribose) Polymerases
  • Calcium