Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer's disease

Neurochemistry International
Matthew R HyndPeter R Dodd

Abstract

Alzheimer's disease (AD) is the most common form of dementia, accounting for 60-70% of cases in subjects over 65 years of age. Several postulates have been put forward that relate AD neuropathology to intellectual and functional impairment. These range from free-radical-induced damage, through cholinergic dysfunction, to beta-amyloid-induced toxicity. However, therapeutic strategies aimed at improving the cognitive symptoms of patients via choline supplementation, cholinergic stimulation or beta-amyloid vaccination, have largely failed. A growing body of evidence suggests that perturbations in systems using the excitatory amino acid L-glutamate (L-Glu) may underlie the pathogenic mechanisms of (e.g.) hypoxia-ischemia, epilepsy, and chronic neurodegenerative disorders such as Huntington's disease and AD. Almost all neurons in the CNS carry the N-methyl-D-aspartate (NMDA) subtype of ionotropic L-glutamate receptors, which can mediate post-synaptic Ca2+ influx. Excitotoxicity resulting from excessive activation of NMDA receptors may enhance the localized vulnerability of neurons in a manner consistent with AD neuropathology, as a consequence of an altered regional distribution of NMDA receptor subtypes. This review discusses mecha...Continue Reading

Citations

Sep 12, 2012·Naunyn-Schmiedeberg's Archives of Pharmacology·Fuka OikawaKunio Ishii
Sep 13, 2007·Analytical and Bioanalytical Chemistry·S M Zakir HossainHiromi Kitano
Jun 23, 2012·Analytical and Bioanalytical Chemistry·Ying LiuAleksandr L Simonian
Nov 30, 2012·European Archives of Psychiatry and Clinical Neuroscience·Markus J SchwarzHarald Hampel
Jun 10, 2010·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Sebastian ThalerTomasz Zarnowski
Sep 1, 2011·Cell and Tissue Research·Filippo CaraciAgata Copani
Nov 1, 2007·Bulletin of Experimental Biology and Medicine·T V DavydovaO A Doronina
Aug 26, 2009·Bulletin of Experimental Biology and Medicine·T V DavydovaI V Maksunova
Aug 7, 2012·Current Neurology and Neuroscience Reports·Gladys E Maestre
Nov 23, 2011·Journal of Molecular Neuroscience : MN·Shlomo SragovichEsther Zoref-Shani
Jun 24, 2008·Chemico-biological Interactions·S AkasofuH Ogura
Feb 23, 2011·The British Journal of Nutrition·David A CamfieldCon Stough
Nov 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Neng-Wei HuMichael J Rowan
May 3, 2008·The Journal of Biological Chemistry·Marie L Blanke, Antonius M J VanDongen
Dec 15, 2005·Neuropsychological Rehabilitation·E B CooperJ B Cooper
Aug 19, 2009·Antioxidants & Redox Signaling·Rukhsana SultanaD Allan Butterfield
Sep 9, 2009·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·Justin P RidgePeter R Dodd
Jul 14, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Olena Y GlushakovaStefania Mondello
Jun 15, 2006·Alzheimer Disease and Associated Disorders·Akinori Akaike
Aug 9, 2011·Sports Medicine and Arthroscopy Review·Nicola MaffulliVincenzo Denaro
Apr 6, 2011·Molecular Pharmacology·Kinning PoonRobert E Oswald
Feb 28, 2008·Dementia and Geriatric Cognitive Disorders·Davide SeripaAlberto Pilotto
Mar 9, 2007·Genome Biology·Erin L HeinzenDavid B Goldstein

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