An axon regeneration signature in a Charcot-Marie-Tooth Disease Type 2 patient

摘要

Charcot-Marie-Tooth Disease (CMT) is one of the most common inherited peripheral neuropathies. The underlying mutations in demyelinating forms tend to affect genes expressed in Schwann cells (CMT Types 1, 3 and 4), while axonal forms of the disease usually have their origins in genes expressed in the affected neurons (CMT Type 2). Repeated rounds of nerve degeneration and regeneration characterize CMT2, but evidence for regeneration has not been demonstrated at a molecular level. Subtractive hybridization was performed on sural nerve biopsies from a patient presenting an axonal form of CMT and an unaffected sibling, which revealed over-expression of genes associated with the regeneration of axons, including PMP22, SPARC/osteonectin, CD9, CD44, EEF1A1 and γ-actin. These results suggest that axonal degeneration elicits a regeneration transcriptional response in the surrounding Schwann cells. This response contrasts with other neurodegenerative diseases in which programmed cell death or an inappropriate immune response are activated. Additionally, Lamin A/C, which is mutated in CMT2B1, was over-expressed in the patient, suggesting that CMT-causing genes may interact in a regulatory network.