Developmental Neuroscience 23:4-5:2001,
377-386.
Andrea Viehover (a), Robert H. Miller
(b), Song-Kyu Park (a), Gerald Fischbach (c), Timothy Vartanian (a)
(a) Department of Neurology, Beth
Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass.,
(b) Department of Neuroscience,
Case Western Reserve University, Cleveland, Ohio, and
(c) Office of the Dean Columbia
University, College of Physicians and Surgeons, New York, N.Y., USA
Abstract
Multiple sclerosis (MS) is an inflammatory
demyelinating disease of the central nervous system (CNS) which results
in demyelination and axonal injury.
Conventional therapy for MS is immune
suppression in the absence of agents that promote neural and glial survival
or remyelination.
Neuregulins are a family of ligands
that exert trophic effects on both neurons and glia.
Using mice bearing a null mutation
in the neuregulin gene, here we demonstrate that neuregulins are necessary
for the normal development of oligodendrocytes.
In addition, neuregulins are produced
in the normal human CNS by astrocytes as well as neurons.
Astrocyte-derived neuregulin is functionally
active in bioassays and exists in secreted and membrane-associated -isoforms.
In active and chronic active MS lesions,
however, the expression of astrocyte neuregulin is dramatically reduced.
The absence of neuregulin in active
MS lesions may contribute to the paucity of remyelination in MS.
Copyright © 2001 S. Karger AG,
Basel