title: XIAP protects oligodendrocytes against cell death in vitro but has no functional role in toxic demyelination.
abstract: Oligodendroglial damage and loss are typical characteristics of demyelinating diseases such as multiple sclerosis (MS) and the leukodystrophies. Axonal loss is the underlying cause of permanent neurological deficits in MS and it is thought to arise from a combination of immune-mediated axonal damage and the loss of trophic support to axons from myelin sheaths after demyelination. Prevention of oligodendroglial damage or death and demyelination are therefore attractive neuroprotective treatment strategies. However, a better understanding of mechanisms leading to oligodendroglial damage and demyelination is a prerequisite for the development of such treatment options. Here, we demonstrate that X-linked inhibitor of apoptosis (XIAP), the most potent member of the inhibitor of apoptosis proteins (IAP) family is expressed in oligodendrocytes in vivo and in vitro. Increased expression of XIAP is associated with protection against selected cell death pathways, whereas decreased expression increases oligodendroglial cell death in vitro. However, lack of XIAP does not modulate oligodendroglial cell death in toxic demyelination in vivo.
authors: Institute of Neuropathology, University Hospital Münster, Domagkstr. 19, Münster, Germany.
authors: Amke
authors: A
authors: Rena Hesse
authors: Karin
authors: K
authors: Hagemeier
authors: Alexander
authors: A
authors: Lürbke
authors: Jasmin
authors: J
authors: Held
authors: Hana
authors: H
authors: Friedman
authors: Alan
authors: A
authors: Peterson
authors: Wolfgang
authors: W
authors: Brück
authors: Tanja
authors: T
authors: Kuhlmann
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D002614:Chelating Agents / Q000633:toxicity; D003471:Cuprizone / Q000633:toxicity; D019610:Cytoprotection / Q000187:drug effects / Q000235:genetics*; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D061251:Primary Cell Culture; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*
chemical_list: D002614:Chelating Agents; D051636:X-Linked Inhibitor of Apoptosis Protein; D003471:Cuprizone