Alzheimer's disease and acetylcholine receptors
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Cholinergic abnormalities, alongside senile plaques, neurofibrillary tangles, and extensive neuronal loss, are the major characteristics in Alzheimer's disease (AD). Both nicotinic and muscarinic acetylcholine receptors are decreased in AD, and it has been shown that the reduction in the number of acetylcholine receptors precedes other pathologic changes. Anti-cholinergic drugs induce amnesia, which can be reversed by withdrawal of the medication. Inhibition of the down-regulation of acetylcholine is, therefore, a strategy for the treatment of AD because it could augment acetylcholine levels within synaptic clefts. In this context, acetylcholinesterase inhibitors, which improve cognitive functions, are currently approved for the treatment of AD. Stimulation of acetylcholine receptors, nicotinic or muscarinic, is another strategy; some drugs are currently under investigation, and reported to be effective. In addition, nicotinic stimulation exerts a neuroprotective effect, and reduces the amyloid burden. Cholinergic therapy may counter the symptoms and progress of AD.
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S. Shimohama, Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaharacho, Sakyoku, Kyoto 606-8507, Japan