axonal atrophy in CMT 1 research from URTV, Italy

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Research from J Peripher Nerv Syst. 2004 Jun;9(2):120.

Down-regulation of receptors for semaphorins and VEGF in a transgenic

model of CMT1A.

Panico M, Palumbo C, Vigo T, Nobbio L, Pisani V, Terracciano C, Schenone

A, Modesti A, Massa R.

Dipartmenti di Neuroscienze, Universita di Roma-Tor Vergata, Italy.

Charcot-Marie-Tooth type 1 disease (CMT1) encompasses a group of primary

demyelinating polyneuropathies caused by molecular defects of the

Schwann cells (SC). Beside myelin damage, axonal atrophy and

degeneration are invariably present and correlate with clinical

severity. This is expected, since signals derived from SC regulate

several axonal properties in myelinated fibers. However, the molecular

mechanisms leading to axonal loss in CMT1 are still obscure. An

important role in promoting axonal growth, guidance and fasciculation in

peripheral nerve (PN) is played by semaphorins and the vascular

endothelial growth factor (VEGF), by binding with specific receptors,

the neuropilins (NP) and VEGF receptors (VEGFR). These molecules are

expressed by peripheral neurons and SC, and induced in these cells

during Wallerian degeneration. We have utilized a transgenic rat model

of CMT1A to assess the immunoreactivity for NP and VEGFR in PN affected

by PMP22 overdosage. These rats, in the hemizygote condition, show

hypo/demyelination and axonal atrophy in PN. In the sciatic nerve of

young hemizygotes we observed a substantial decrease of immunoreactivity

for NP1 and VEGFR2, both in myelinated axons and SC, as compared to

controls. Conversely, NP2 expression was slightly reduced. These data

show that a down-regulation of the semaphorin/neuropilin and VEGF

signalling pathways may take place in CMT1. Such event may play a

causative role in the axonal atrophy observed in this group of

disorders.