TY - JOUR
T1 - Excitotoxic neurodegeneration in Alzheimer disease
T2 - New hypothesis and new therapeutic strategies
AU - Olney, John W.
AU - Wozniak, David F.
AU - Farber, Nuri B.
PY - 1997/10
Y1 - 1997/10
N2 - We have described a novel excitotoxic process potentially relevant to AD in which hypofunctional NMDA receptors cease driving GABAergic neurons that cease inhibiting the 2 major excitatory transmitters in the brain (glutamate and acetylcholine), and these disinhibited excitatory transmitters then act in concert to slowly hyperstimulate neurons in corticolimbic brain regions to death. Accepting this hypothesis that features a multisystem network disturbance that can explain how a corticolimbic pattern of neurodegenerative events is triggered in AD does not require abandoning other candidate mechanisms. For example, genetic hypotheses that focus primarily on amyloid processing or deposition are compatible with our hypothesis and would gain in explanatory power if combined with our hypothesis. If our hypothesis is correct, it may provide valuable new therapeutic approaches to AD.
AB - We have described a novel excitotoxic process potentially relevant to AD in which hypofunctional NMDA receptors cease driving GABAergic neurons that cease inhibiting the 2 major excitatory transmitters in the brain (glutamate and acetylcholine), and these disinhibited excitatory transmitters then act in concert to slowly hyperstimulate neurons in corticolimbic brain regions to death. Accepting this hypothesis that features a multisystem network disturbance that can explain how a corticolimbic pattern of neurodegenerative events is triggered in AD does not require abandoning other candidate mechanisms. For example, genetic hypotheses that focus primarily on amyloid processing or deposition are compatible with our hypothesis and would gain in explanatory power if combined with our hypothesis. If our hypothesis is correct, it may provide valuable new therapeutic approaches to AD.
UR - http://www.scopus.com/inward/record.url?scp=0030782939&partnerID=8YFLogxK
U2 - 10.1001/archneur.1997.00550220042012
DO - 10.1001/archneur.1997.00550220042012
M3 - Article
C2 - 9341569
AN - SCOPUS:0030782939
SN - 0003-9942
VL - 54
SP - 1234
EP - 1240
JO - Archives of neurology
JF - Archives of neurology
IS - 10
ER -