Neuronal nicotinic acetylcholine receptors: involvement in Alzheimer's disease and schizophrenia.
Nicotinic acetylcholine receptors (nAChRs) play a role in a variety of diseases of the central nervous system including Alzheimer's disease (AD) and schizophrenia. There is great interest in evaluating disease-related nA ChR changes, and pharmacological treatment of nAChR deficits is a promising therapy. In AD, 7 nAChRs remain relatively stable, contrasting to 4 2 nAChRs that are lost in substantial numbers. -amyloid, a major neuropathology in AD, blocks 4 2 and 7 nAChRs. Agonists selective to 7nAChRs are neuroprotective against--amyloid. Paradoxically, 7nAChRs may function as receptors for -amyloid. These results indicate 7 nAChR antagonists may be appropriate therapy in AD. In schizophrenia, 7 nAChRs are significantly reduced in hippocampus and neocortex. The exceptionally high rate of smoking in schizophrenics is likely a form of self-medication. Therapy with 7 nAChR agonists relieves some schizophrenic symptoms. Despite disparities in etiology and symptomatology, AD and schizophrenia share a target for therapeutic intervention--7 nAChRs.
Woodruff-Pak
Diana S
DS
Temple University and Albert Einstein Healthcare Network, USA.
Gould
Thomas J
TJ
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001245:Association Learning / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D011817:Rabbits; D011978:Receptors, Nicotinic / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D011978:Receptors, Nicotinic