CMT 1 and 4 Mechanisms of Disease: inherited demyelinating neuropathies-from bas

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Nat Clin Pract Neurol. 2007 Aug;3(8):453-464.

Mechanisms of Disease: inherited demyelinating neuropathies-from

basic to clinical research.

Nave KA, Sereda MW, Ehrenreich H.

K-A Nave is the Director of the Department of Neurogenetics and MW

Sereda is a Neurologist in the Departments of Neurology and Clinical

Neurophysiology, University of Göttingen, and Junior Group Leader at

the Max Planck Institute of Experimental Medicine. H Ehrenreich is

Professor of Psychiatry and Neurology at the Max Planck Institute of

Experimental Medicine and the University of Göttingen, Göttingen,

Germany.

The hereditary motor and sensory neuropathies (also known as Charcot-

Marie-Tooth disease or CMT) are characterized by a length-dependent

loss of axonal integrity in the PNS, which leads to progressive

muscle weakness and sensory deficits. The 'demyelinating'

neuropathies (CMT disease types 1 and 4) are genetically

heterogeneous, but the their common feature is that the primary

defect perturbs myelination. As we discuss in this Review, several

new genes associated with CMT1 and CMT4 have recently been

identified.

The emerging view is that a range of different subcellular defects

in Schwann cells can cause axonal loss, which represents the final

common pathway of all CMT disease and is independent of

demyelination.

We propose that Schwann cells provide a first line of axonal

neuroprotection. A better understanding of axon-glia interactions

should open the way to therapeutic interventions for demyelinating

neuropathies. Transgenic animal models have become essential for

dissecting CMT disease mechanisms and exploring novel therapies.