Semaphorin 3A and 3F: key players in myelin repair in multiple sclerosis?
The presence of demyelinated plaques in the central nervous system is the hallmark of multiple sclerosis (MS). Some plaques remyelinate but others do not, leaving permanent damage. The reasons for this failure of repair are many, but one possible reason is the lack of migration of oligodendrocyte precursor cells to the lesion. The guidance molecules Semaphorin 3A and 3F, already known to direct oligodendroglial migration in development, may also be active in controlling oligodendrocyte precursor cell migration in MS, and hence may determine the ability of plaques to remyelinate. Here, in MS tissue and an experimental model of demyelination, we demonstrate a local source of these molecules around active demyelinating lesions, but not chronic plaques. We also provide evidence for their up-regulation at a distance from the lesion, in the neuronal cell bodies corresponding to the demyelinated axons. We propose that both of these mechanisms influence remyelination.
Williams
Anna
A
Inserm, U711, Paris, F-75013 and Université Pierre & Marie Curie, Faculté de médecine, IFR 70, Paris, France. annacwilliwams@yahoo.co.uk
Piaton
Gabrièle
G
Aigrot
Marie-Stéphane
MS
Belhadi
Aisha
A
Théaudin
Marie
M
Petermann
Franziska
F
Thomas
Jean-Léon
JL
Zalc
Bernard
B
Lubetzki
Catherine
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D002540:Cerebral Cortex / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009186:Myelin Sheath / Q000378:metabolism* / Q000502:physiology; D009416:Nerve Regeneration; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D040121:Semaphorin-3A / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D015854:Up-Regulation
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C108639:SEMA3A protein, human; C491230:SEMA3F protein, human; C506913:Sema3F protein, rat; C488218:Sema3a protein, rat; D040121:Semaphorin-3A