＜シンポジウム19―3＞グリア細胞と神経疾患
脱髄とオリゴデンドロサイト
伊藤 高行, 堀内 真, 若山 幸示, 伊藤 あき, David Pleasure
University of California Davis, Dept. of Neurology/Shriners Hospitals for Children Northern California[2425 Stockton Boulevard, Sacramento, CA95817, USA]
Although neurological sequelae are attributable to poor regeneration of the central nervous system, oligodendrocytes demonstrate robust regenerative response even in adults. Accumulating evidence indicates that the glial cells identified by surface expression of the proteoglycan NG2 are the cellular source of newly-developed oligodendrocytes following demyelination, and thereby considered adult oligodendroglial progenitor cells (OPCs). Despite their robust regenerative capability, remyelination often ends up in failure or is incomplete, particularly after recurrent neuroinflammation, which is referred to as "remyelination failure". While axonal degeneration may contribute to remyelination failure, OPCs are also affected by neuroinflammation. Indeed, various studies have indicated that gamma-interferon, a proinflammatory cytokine associated with autoimmunity, is cytotoxic to OPCs by inducing cell death, and inhibiting their proliferation and differentiation. In contrast to gamma-interferon, we confirmed that beta-interferon which is used for the treatment of relapsing-remitting multiple sclerosis does not induce OPC death. Through a comprehensive analysis of gamma-interferon-inducible and beta-interferon-inducible genes in OPCs, we have identified interferon regulatory factor-1 and -8 (IRF1 and IRF8) as candidate transcription factors responsible for gamma-interferon-mediated cytotoxicity in OPCs. Validating and elaborating on these findings particularly in in vivo models may prove of importance in understanding remyelination failure and suggest therapeutic approaches to enhance remyelination.
Full Text of this Article in Japanese PDF (343K)
(臨床神経, 51：1036−1039, 2011)
key words：多発性硬化症，オリゴデンドロサイト，インターフェロン，髄鞘再生不全，Interferon regulatory factor
（受付日：2011年5月20日）
