title: 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.
authors.affiliation: Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK. m.duchen@ucl.ac.uk
authors.forename: Michael R
authors.initials: MR
authors.lastname: Duchen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D016923:Cell Death; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D019636:Neurodegenerative Diseases / Q000209:etiology*; D009474:Neurons / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D011065:Poly(ADP-ribose) Polymerases; D002118:Calcium