INVITED REVIEW Mitochondria, calcium-dependent neuronal death and neurodegenerative disease

Abstract Understanding the mechanisms of neuronal dys-function 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 dis-eases. 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 rep-resent 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 inMotoneuron 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 mech-anisms of calcium-dependent mitochondrial-mediated cell death