Affiliations: Department of Anatomy, Neuroanatomy, University of Köln, D-50931 Köln, Germany
Correspondence:
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Corresponding author: Dr. Andrea Wevers, Institut II für Anatomie, Universität zu Köln, Joseph-Stelzmann Str. 9, D-50931 Köln, F.R. Germany, Tel.: +49 221 478 5957, Fax: +49 221 478 5318, E-mail: wevers.anatomie@uni-koeln.de.
Note: [*] This article is published with permission from the University of Kentucky. It is also published in the online journal Alzheimer's Disease Review; www.coa.uky.edu/ADReview.
Abstract: Nicotinic cholinoceptive dysfunction associated with cognitive impairment is a leading neurochemical feature of Alzheimer's disease. There-fore, nicotinic acetylcholine receptors have attracted considerable interest as potential therapeutic targets. The deficit of nicotine binding sites in Alzheimer's disease may be related to alterations of nicotinic receptor synthesis on the levels of (i) transcription, (ii) translation and post-translational modifications, (iii) receptor transport and turnover, including membrane insertion. Current approaches aim at the elucidation of molecular changes at all three levels. Although a com-prehensive picture has not yet been achieved, currently available data can be summarized as follows: (i) there are no changes at the level of transcription of subunit mRNAs studied so far, (ii) evidence is accumulating for a distinct decrease on the protein level in the expression especially of the α4-subunit, and (iii) preliminary findings point to a possible correlation of cytoskeletal changes (hyperphosphorylation of ô-protein) with decreased nicotinic acetylcholine receptor expression.
