, Volume 464, Issue 1, pp 111-121,
Open Access This content is freely available online to anyone, anywhere at any time.
Date: 22 May 2012

Mitochondria, calcium-dependent neuronal death and neurodegenerative disease

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.

This article is published as part of the special issue on “Cell-specific roles of mitochondrial Ca2+ handling.”