Altered neurofilament phosphorylation and beta tubulin isotypes in Charcot-Marie-Tooth disease type 1

• Published in: Neurology Vol. 44; no. 12; p. 2383
• Main Authors: Watson, D F, Nachtman, F N, Kuncl, R W, Griffin, J W
• Format: Journal Article
• Language: English
• Published: United States 01.12.1994
• Subjects: Adolescent; Adult; Aged; Atrophy; Axons - metabolism; Axons - pathology; Biopsy; Charcot-Marie-Tooth Disease - metabolism; Charcot-Marie-Tooth Disease - pathology; Child; Cytoskeletal Proteins - analysis; Cytoskeletal Proteins - metabolism; Humans; Middle Aged; Nervous System Diseases - metabolism; Nervous System Diseases - pathology; Neurofilament Proteins - analysis; Neurofilament Proteins - metabolism; Phosphorylation; Reference Values; Sural Nerve - metabolism; Sural Nerve - pathology; Tubulin - analysis; Tubulin - metabolism
• ISSN: 0028-3878
• DOI: 10.1212/wnl.44.12.2383

Charcot-Marie-Tooth disease type 1 (CMT1) is associated with atrophy and degeneration of peripheral nerve axons in addition to prominent changes in the structure of Schwann cells. We have investigated the composition of the axonal cytoskeleton in sural nerve biopsies from patients with CMT1. Compared to controls, CMT1 nerves exhibited marked hypophosphorylation of neurofilament proteins and an increased relative abundance of beta tubulin isotypes 2 and 3. Biopsies from patients with other causes of neuropathy, matched to the CMT1 group for severity of axonal atrophy, exhibited an intermediate degree of neurofilament hypophosphorylation and no abnormality of tubulin isotypes. The axonal cytoskeleton in CMT1 resembles that of immature nerve fibers. A failure of normal Schwann cell-axon interaction in CMT1 may prevent full differentiation of the axonal cytoskeleton of myelinated nerve fibers.