Modulation of beta-amyloid precursor protein processing and tau phosphorylation by acetylcholine receptors.
Neurofibrillary lesions and senile plaques that are composed mainly of hyperphosphorylated tau protein and the amyloid-beta peptide derived from the amyloid precursor protein, respectively, are classical hallmarks of Alzheimer's disease. A number of studies strongly suggests that amyloid-beta formation and amyloid depositions are linked to the pathogenesis of Alzheimer's disease. Recent findings suggest that very low concentrations of the amyloid-beta can inhibit various cholinergic neurotransmitter functions independently of apparent neurotoxicity. Many factors have been shown to influence the processing of amyloid precursor protein, including activation of muscarinic and nicotinic receptors. This review focus on some recent studies concerning the regulation of amyloid precursor protein processing and modulation of tau phosphorylation by acetylcholine receptor stimulation and how cholinergic deficits and amyloid-beta might be related to one another.
Hellström-Lindahl
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Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research, Division of Molecular Neuropharmacology, Karolinska Institutet, Huddinge University Hospital, Sweden. ewa.hellstrom-lindahl@kfcmail.hs.sll.se
D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010766:Phosphorylation; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism; D012907:Smoking / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D018722:Nicotinic Agonists; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D016875:tau Proteins; D009538:Nicotine