title: Overexpression of ErbB2 and ErbB3 receptors in Schwann cells of patients with Charcot-Marie-tooth disease type 1A.
abstract: Axon-derived neuregulins (NRGs) are a family of growth factors whose binding to ErbB tyrosine kinase receptors promotes the maturation, proliferation and survival of Schwann cells (SCs). Correct NRG/ErbB signaling is essential for the homeostasis of axonal-glial complexes and seems to play a role in peripheral nerve repair. The potential involvement of ErbB receptors in human peripheral neuropathies has not been clarified. Therefore, we assessed the immunoreactivity for EGFR (ErbB1), ErbB2, and ErbB3 in nerve biopsies from patients with different forms of Charcot-Marie-Tooth disease, type 1, (CMT1), as compared to others with inflammatory neuropathies and controls. The most notable changes consisted in the overexpression of ErbB2 and ErbB3 by SCs of nerves from CMT1A patients. These findings are consistent with an impairment of SC differentiation and expand the molecular phenotype of CMT1A. The upregulation of these receptors may play a role in the inhibition of myelination or in the promotion of recurrent demyelination and axonal damage.
authors.affiliation: Dipartimento di Neuroscienze, Università di Roma Tor Vergata, Via Montpellier 1, I-00133 Roma, Italy. massa@uniroma.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Massa
authors.forename: Camilla
authors.initials: C
authors.lastname: Palumbo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cavallaro
authors.forename: Maria Beatrice
authors.initials: MB
authors.lastname: Panico
authors.forename: Roberto
authors.initials: R
authors.lastname: Bei
authors.forename: Chiara
authors.initials: C
authors.lastname: Terracciano
authors.forename: Nicolò
authors.initials: N
authors.lastname: Rizzuto
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Andrea
authors.initials: A
authors.lastname: Modesti
mesh_terms: D000818:Animals; D019771:Axotomy; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D017630:Connexins / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020893:Receptor, ErbB-3 / Q000096:biosynthesis / Q000235:genetics*; D012583:Schwann Cells / Q000378:metabolism*; D012584:Sciatic Nerve / Q000502:physiology; D013497:Sural Nerve / Q000473:pathology; D014855:Wallerian Degeneration / Q000503:physiopathology; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D020893:Receptor, ErbB-3; D000097002:Gap Junction beta-1 Protein