Parkinson's disease, Alzheimer's disease and motor neurone disease: identifying a common mechanism.
Although Alzheimer's disease, Parkinson's disease, and motor neurone disease are distinct disorders, there could be a common neurodegenerative mechanism that characterises the death of selective neurone populations in each case. We propose that this mechanism could be an aberrantly activated, developmental process involving a non-classical, non-enzymatic action of acetylcholinesterase mediated via a short linear motif near the C-terminal end of the molecule. Since this motif has a highly conserved homology with part of the amyloid precursor protein, it may be particularly attractive as a target for novel therapeutic strategies in neurodegeneration.
Greenfield
S
S
University Department of Pharmacology, Mansfield Road, OX1 3QT, Oxford, UK. susan.greenfield@pharmacology.ox.ac.uk
Vaux
D J
DJ
D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism*; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D016923:Cell Death; D006801:Humans; D008969:Molecular Sequence Data; D016472:Motor Neuron Disease / Q000201:enzymology / Q000378:metabolism*; D010300:Parkinson Disease / Q000201:enzymology / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D000110:Acetylcholinesterase