Neuregulin: an oligodendrocyte growth factor absent in active multiple sclerosis lesions.
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 beta-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.
Viehover
A
A
Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Miller
R H
RH
Park
S K
SK
Fischbach
G
G
Vartanian
T
T
D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D005333:Fetus; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000235:genetics*; D020880:Neuregulins / Q000172:deficiency* / Q000235:genetics; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D016548:Prosencephalon; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D005904:Glial Fibrillary Acidic Protein; D020880:Neuregulins; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C075278:platelet-derived growth factor A