TAILIEUCHUNG - Báo cáo khoa học: Non-hydrolytic functions of acetylcholinesterase The significance of C-terminal peptides

This review explores the possibility that acetylcholinesterase may play a pivotal, non-hydrolytic role in neurodegeneration. More specifically, C-ter-minal sequences of acetylcholinesterase may act as signalling molecules in key brain regions characteristically vulnerable to Alzheimer’s, Parkinson’s and motor neuron disease. | MINIREVIEW Non-hydrolytic functions of acetylcholinesterase The significance of C-terminal peptides Susan A. Greenfield Martina Zimmermann and Cherie E. Bond The Institute for the Future of the Mind Oxford University UK Keywords Alzheimer s degeneration development globalneurons motor neuron disease nicotinic receptor oxidative stress Parkinson s substrate inhibition trophic-toxic axis This review explores the possibility that acetylcholinesterase may play a pivotal non-hydrolytic role in neurodegeneration. More specifically C-ter-minal sequences of acetylcholinesterase may act as signalling molecules in key brain regions characteristically vulnerable to Alzheimer s Parkinson s and motor neuron disease. Correspondence M. Zimmermann Max-von-Laue Strasse 9 Biocenter N260 Johann Wolfgang Goethe University 60438 Frankfurt am Main Germany E-mail . uk Received 12 September 2007 accepted 12 December 2007 doi The idea that acetylcholinesterase might have actions independent of the hydrolysis of its familiar substrate acetylcholine is far from new the evidence subsequently supporting this suggestion is comprehensively reviewed elsewhere in this minireview series and thus need not be reiterated here. Nonetheless two particular features of a non-enzymatic role need noting. First acetylcholinesterase is not only present in neurons using transmitters such as dopamine noradrenaline and serotonin but second is actually secreted in a soluble form from these cells 1 2 . What might be its function therefore as an intercellular messenger in its own right Interestingly enough the groups of aminergic neurons characterized by the storage and release of acetylcholinesterase cluster together in a continuous hub extending the length of the brainstem - motor neurons locus coeruleus raphe nuclei and substantia nigra ven-tral tegmental area up to the basal forebrain. Despite the heterogeneity in transmitters these different nuclei

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