Axonopathy and cytoskeletal disruption in degenerative diseases of the central nervous system.
There has been growing interest in the axon as the initial focus of pathological change in a number of neurodegenerative diseases of the central nervous system. This review concentrates on three major neurodegenerative conditions--amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer's disease--with emphasis on key cellular changes that may underlie early axonal dysfunction and pathology and, potentially, the degeneration of neurons. In particular, this review will address recent data that indicate that the main pathological stimuli for these conditions, though often not definitively determined, result in an initial perturbation of the axon and its cytoskeleton, which then results in slow neuronal degeneration and loss of connectivity. The identification of a degenerative process initiated in the axon may provide new therapeutic targets for early intervention to inhibit the grim outcomes related to the progression of these diseases.
Vickers
James C
JC
NeuroRepair Group and Wicking Dementia Research and Education Centre, Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia. James.Vickers@utas.edu.au
King
Anna E
AE
Woodhouse
Adele
A
Kirkcaldie
Matthew T
MT
Staal
Jerome A
JA
McCormack
Graeme H
GH
Blizzard
Catherine A
CA
Musgrove
Ruth E J
RE
Mitew
Stanislaw
S
Liu
Yao
Y
Chuckowree
Jyoti A
JA
Bibari
Olivier
O
Dickson
Tracey C
TC
D000544:Alzheimer Disease / Q000473:pathology*; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D001369:Axons / Q000473:pathology*; D003599:Cytoskeleton / Q000473:pathology*; D006801:Humans; D009103:Multiple Sclerosis / Q000473:pathology*