Intermediate Filaments/mentions CMT Type 2E

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Abstract from J Neurobiol. 2004 Jan;58(1):131-48.

Functions of intermediate filaments in neuronal development and disease.

Lariviere RC, n JP.

Centre for Research in Neurosciences, Research Institute of the McGill

University Health Centre, Montreal General Hospital, Montreal, Quebec,

Canada.

Five major types of intermediate filament (IF) proteins are expressed in

mature neurons: the three neurofilament proteins (NF-L, NF-M, and NF-H),

alpha-internexin, and peripherin. While the differential expression of

IF genes during embryonic development suggests potential functions of

these proteins in axogenesis, none of the IF gene knockout experiments

in mice caused gross developmental defects of the nervous system. Yet,

deficiencies in neuronal IF proteins are not completely innocuous.

Substantial developmental loss of motor axons was detected in mice

lacking NF-L and in double knockout NF-M;NF-H mice, supporting the view

of a role for IFs in axon stabilization. Moreover, the absence of

peripherin resulted in approximately 30% loss of small sensory axons.

Mice lacking NF-L had a scarcity of IF structures and exhibited a severe

axonal hypotrophy, causing up to 50% reduction in conduction velocity, a

feature that would be very detrimental for large animal species.

Unexpectedly, the NF-M rather than NF-H protein turned out to be

required for proper radial growth of large myelinated axons. Studies

with transgenic mice suggest that some types of IF accumulations,

reminiscent of those found in amyotrophic lateral sclerosis (ALS), can

have deleterious effects and even cause neurodegeneration. Additional

evidence for the involvement of IFs in pathogenesis came from the recent

discovery of neurofilament gene mutations linked to ALS and

Charcot-Marie-Tooth disease (CMT2E). Conversely, we discuss how certain

types of perikaryal neurofilament aggregates might confer protection in

motor neuron disease.