Neuronal Nicotinic Acetylcholine Receptors: Involvement in Alzheimer’s Disease and Schizophrenia

Abstract

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 nAChR 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 7 nAChRs are neuroprotective against amyloid. Paradoxically, 7 nAChRs 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.