Charcot-Marie-Tooth disease: an update : Current Opinion in Neurology (original) (raw)

Neuromuscular disease: nerve

Departments of Neurology and Molecular Medicine and Genetics, Wayne State University, School of Medicine, Detroit, Michigan, USA

Correspondence to Michael E. Shy, MD, Wayne State University, School of Medicine, 421 East Canfield, Elliman Building 3206, Detroit, MI 48201, USA Tel: +1 313 577 6903; fax: +1 313 577 7552; e-mail: [email protected]

Abbreviations

ALS: amyotrophic lateral sclerosis

CMT: Charcot-Marie-Tooth disease

CNS: central nervous system

dHMN: distal hereditary motor neuropathy

HNPP: hereditary neuropathy with liability to pressure palsies

NCV: nerve conduction velocity

PNS: peripheral nervous system

sHSP: small heat-shock protein

Abstract

Purpose of review

The purpose of this review is to assist neurologists, neuroscientists and other interested readers in following the expanding volume of information relating to the inherited peripheral neuropathies collectively referred to as Charcot-Marie-Tooth disease. Currently, mutations in multiple different genes expressed in Schwann cells and neurons cause a variety of overlapping clinical phenotypes.

Recent findings

Recent articles clarify molecular pathways involved in the pathogenesis of these disorders, and for the first time provide rational treatment strategies for the most common form of Charcot-Marie-Tooth disease. The identification of many new genes associated with neuropathy demonstrate the role of axonal transport and abnormal protein trafficking in causing various forms of Charcot-Marie-Tooth. They also further define the role of axonal signaling and the molecular architecture of both Schwann cells and neurons in maintaining normal peripheral nervous system function. Finally, recent reports have shown that progesterone antagonists and ascorbic acid can successfully treat rodent models of Charcot-Marie-Tooth disease type 1A.

Summary

Taken together, results from these articles support the concept that genetic causes of Charcot-Marie-Tooth disease serve as a living microarray system to identify molecules necessary for normal peripheral nervous system function. When we can make sense of these microarrays we are likely to understand the pathogenesis and develop rational therapies for many neurodegenerative diseases including Charcot-Marie-Tooth.