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S100B is increased in Parkinson's disease and ablation protects against MPTP-induced toxicity through the RAGE and TNF-? pathway.


ABSTRACT: Parkinson's disease is a neurodegenerative disorder that can, at least partly, be mimicked by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. S100B is a calcium-binding protein expressed in, and secreted by, astrocytes. There is increasing evidence that S100B acts as a cytokine or damage-associated molecular pattern protein not only in inflammatory but also in neurodegenerative diseases. In this study, we show that S100B protein levels were higher in post-mortem substantia nigra of patients with Parkinson's disease compared with control tissue, and cerebrospinal fluid S100B levels were higher in a large cohort of patients with Parkinson's disease compared with controls. Correspondingly, mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine showed upregulated S100B messenger RNA and protein levels. In turn, ablation of S100B resulted in neuroprotection, reduced microgliosis and reduced expression of both the receptor for advanced glycation endproducts and tumour necrosis factor-?. Our results demonstrate a role of S100B in the pathophysiology of Parkinson's disease. Targeting S100B may emerge as a potential treatment strategy in this disorder.

SUBMITTER: Sathe K 

PROVIDER: S-EPMC3501971 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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S100B is increased in Parkinson's disease and ablation protects against MPTP-induced toxicity through the RAGE and TNF-α pathway.

Sathe Kinnari K   Maetzler Walter W   Lang Johannes D JD   Mounsey Ross B RB   Fleckenstein Corina C   Martin Heather L HL   Schulte Claudia C   Mustafa Sarah S   Synofzik Matthis M   Vukovic Zvonimir Z   Itohara Shigeyoshi S   Berg Daniela D   Teismann Peter P  

Brain : a journal of neurology 20121101 Pt 11


Parkinson's disease is a neurodegenerative disorder that can, at least partly, be mimicked by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. S100B is a calcium-binding protein expressed in, and secreted by, astrocytes. There is increasing evidence that S100B acts as a cytokine or damage-associated molecular pattern protein not only in inflammatory but also in neurodegenerative diseases. In this study, we show that S100B protein levels were higher in post-mortem substantia nigra of  ...[more]

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