3.8 Article

The amount of sonic hedgehog in multiple sclerosis white matter is decreased and cleavage to the signaling peptide is deficient

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MULTIPLE SCLEROSIS
卷 9, 期 4, 页码 362-371

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ARNOLD, HODDER HEADLINE PLC
DOI: 10.1191/1352458503ms924oa

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multiple sclerosis; myelin basic protein; neurodegenerative disease; sonic hedgehog

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We have demonstrated that sonic hedgehog (Shh), vital for oligodendrocyte development, is present in both gray and white matter of normal human brain. Both the 45 kDa precursor protein and the 20 kDa N-terminal sonic hedgehog signaling portion ( ShhN) were demonstrated by immunoblot and a partial purification has been achieved. In gray matter from brains of multiple sclerosis ( MS) victims, the total amount of Shh was less than normals and the signaling 20 kDa protein was greatly reduced. In white matter homogenates, prepared from MS victims, only the 45 kDa precursor protein was found. None of the 20 kDa signaling protein was detected, suggesting that the 45 kDa signaling protein was not cleaved in the autocatalytic reaction carried out by the C - terminal portion. The 45 kDa protein and a small amount of the 20 kDa ShhN was detected in isolated MS myelin by Western blot, demonstrating some cleavage was possible. The cleavage of the 45 kDa protein was demonstrated in normal myelin in vitro, but not in myelin prepared from MS brain.

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