title: Axonopathy and cytoskeletal disruption in degenerative diseases of the central nervous system.
abstract: 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.
authors.affiliation: NeuroRepair Group and Wicking Dementia Research and Education Centre, Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia. James.Vickers@utas.edu.au
authors.forename: James C
authors.initials: JC
authors.lastname: Vickers
authors.forename: Anna E
authors.initials: AE
authors.lastname: King
authors.forename: Adele
authors.initials: A
authors.lastname: Woodhouse
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Kirkcaldie
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Staal
authors.forename: Graeme H
authors.initials: GH
authors.lastname: McCormack
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Blizzard
authors.forename: Ruth E J
authors.initials: RE
authors.lastname: Musgrove
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Mitew
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.forename: Jyoti A
authors.initials: JA
authors.lastname: Chuckowree
authors.forename: Olivier
authors.initials: O
authors.lastname: Bibari
authors.forename: Tracey C
authors.initials: TC
authors.lastname: Dickson
mesh_terms: 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*