title: Nonselective cation channels and links to hippocampal ischemia, aging, and dementia.
abstract: Stroke is a very strong risk factor for dementia. Furthermore, ischemic stroke and Alzheimer's disease (AD) share a number of overlapping mechanisms of neuron loss and dysfunction, including those induced by the inappropriate activation of N-methyl-D-aspartate receptors (NMDARs). These receptors form a major subtype of excitatory glutamate receptor. They are nonselective cation channels with appreciable Ca(2+) permeability, and their overactivation leads to neurotoxicity in the cortex and hippocampus. NMDARs have therefore been therapeutic targets in both conditions, but they have failed in the treatment of stroke, and there is limited rationale for using them in treating AD. In this chapter, we discuss current understanding of subtypes of NMDARs and their potential roles in -ischemic stroke and AD. We also discuss the properties of several other nonselective cation channels, transient receptor potential melastatin 2 and 7 channels, and their implications in linking these conditions.
authors.affiliation: Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada. jfmacdonald@robarts.ca
authors.forename: John F
authors.initials: JF
authors.lastname: MacDonald
authors.forename: Jillian C
authors.initials: JC
authors.lastname: Belrose
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Xie
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jackson
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017346:Protein Serine-Threonine Kinases; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism / Q000473:pathology; D050053:TRPM Cation Channels / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D050053:TRPM Cation Channels; C475667:TRPM3 protein, human; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D002118:Calcium