Axonal transport of neurofilaments in normal and disease states |
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Authors: | CCJ Miller S Ackerley J Brownlees AJ Grierson NJO Jacobsen P Thornhill |
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Institution: | (1) Departments of Neuroscience and Neurology, The Institute of Psychiatry, Kings College London, De Crespigny Park, Denmark Hill, London SE5 8AF (United Kingdom), Fax +44 (0) 207 7080017, e-mail: chris.miller@iop.kcl.ac.uk, GB;(2) Present address: Academic Neurology Unit, Medical School, University of Sheffield, Sheffield, Yorkshire S10 2RX (United Kingdom), GB;(3) Present address: School of Biochemistry and Molecular Biology, University of Leeds, Leeds, Yorkshire LS2 9JT (United Kingdom), GB |
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Abstract: | Neurofilaments are among the most abundant organelles in neurones. They are synthesised in cell bodies and then transported
into and through axons by a process termed 'slow axonal transport' at a rate that is distinct from that driven by conventional
fast motors. Several recent studies have now demonstrated that this slow rate of transport is actually the consequence of
conventional fast rates of movement that are interrupted by extended pausing. At any one time, most neurofilaments are thus
stationary. Accumulations of neurofilaments are a pathological feature of several human neurodegenerative diseases suggesting
that neurofilament transport is disrupted in disease states. Here, we review recent advances in our understanding of neurofilament
transport in both normal and disease states. Increasing evidence suggests that phosphorylation of neurofilaments is a mechanism
for regulating their transport properties, possibly by promoting their detachment from the motor(s). In some neurodegenerative
diseases, signal transduction mechanisms involving neurofilament kinases and phosphatases may be perturbed leading to disruption
of transport.
Received 11 July 2001; received after revision 30 August 2001; accepted 31 August 2001 |
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Keywords: | , Neurofilaments, phosphorylation, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, axonal,,,,,transport, |
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