HMSN mutations/Schwann cell autonomous phenotype resulting in demyelination with secondary axonal loss

[Guest guest]

Abstract from Neurobiol Dis. 2004 Nov;17(2):290-299.

Expression analysis of the N-Myc downstream-regulated gene 1 indicates

that myelinating Schwann cells are the primary disease target in

hereditary motor and sensory neuropathy-Lom.

Berger P, Sirkowski EE, Scherer SS, Suter U.

Department of Biology, Institute of Cell Biology, Swiss Federal

Institute of Technology, ETH-Honggerberg, CH-8093 Zurich, Switzerland.

Mutations in the gene encoding N-myc downstream-regulated gene-1 (NDRG1)

lead to truncations of the encoded protein and are associated with an

autosomal recessive demyelinating neuropathy-hereditary motor and

sensory neuropathy-Lom. NDRG1 protein is highly expressed in peripheral

nerve and is localized in the cytoplasm of myelinating Schwann cells,

including the paranodes and Schmidt-Lanterman incisures. In contrast,

sensory and motor neurons as well as their axons lack NDRG1. NDRG1 mRNA

levels in developing and injured adult sciatic nerves parallel those of

myelin-related genes, indicating that the expression of NDRG1 in

myelinating Schwann cells is regulated by axonal interactions.

Oligodendrocytes also express NDRG1, and the subtle CNS deficits of

affected patients may result from a lack of NDRG1 in these cells. Our

data predict that the loss of NDRG1 leads to a Schwann cell autonomous

phenotype resulting in demyelination, with secondary axonal loss.