The role of the N-methyl-D-aspartate receptor in Alzheimer's disease: therapeutic potential.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with an unknown etiology. Pathologic processes implicated in AD include b-amyloid-induced synaptic failure; tau hyperphosphorylation; inflammation; oxidative stress; abnormal neurotransmission involving acetylcholine, glutamate, norepinephrine, serotonin, and dopamine; and abnormalities in second messengers, protein kinases, and apoptosis. Although each of these pathways offers potential therapeutic targets, pharmacologic manipulation of the glutamatergic N-methyl-D-aspartate receptor pathway, alone or in combination with cholinergic therapies, is emerging as the next promising strategy for the treatment of AD and vascular dementia.
Doraiswamy
P Murali
PM
Departments of Psychiatry and Medicine, and the Center for the Study of Aging, Duke University Medical Center, Box 3018, Durham, NC 27710, USA. dorai001@mc.duke.edu
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002986:Clinical Trials as Topic; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid