Microtubule-stabilising drugs for therapy of Alzheimer's disease and other neurodegenerative disorders with axonal transport impairments.
Increasing evidence implicates impairments of axonal transport in mechanisms underlying diverse neurodegenerative disease. This evidence includes discoveries of mutations in genes encoding human motor proteins or proteins involved in stabilising the microtubule (MT) network required for maintenance of axonal transport in familial neurodegenerative disorders, as well as data from in vivo and in vitro model systems. Moreover, in sporadic neurodegenerative disorders such as Alzheimer's disease (AD), pathological alterations of the MT-binding protein tau are linked to impaired axonal transport and brain degeneration. Because MT-stabilising compounds hold promise for counteracting the loss of tau function in AD and sustaining effective axonal transport, we conclude that MT-binding/stabilising drugs show potential therapeutic utility for the treatment of AD and other neurodegenerative disorders characterised by altered MTs and impaired axonal transport.
Trojanowski
John Q
JQ
Smith
Amos B
AB
Huryn
Donna
D
Lee
Virginia M-Y
VM
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use
D017239:Paclitaxel