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

Kinnari Sathe, Walter Maetzler, Johannes Lang, Ross Brian Mounsey, Corinna Fleckenstein, Heather Louise Martin, Claudia Schulte, Sarah Mustafa, Matthis Synofzik, Zvonimir Vukovic, Shigeyoshi Itohara, Daniela Berg, Peter Teismann

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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
25 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 CSF 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
30 neuroprotection, reduced microgliosis and reduced expression of both the receptor for advanced glycation endproducts and
tumour necrosis factor-a. 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.
Original languageEnglish
Pages (from-to)3336-3347
Number of pages12
JournalBrain
Volume135
Issue number11
DOIs
Publication statusPublished - Nov 2012

Keywords

  • calcium-binding protein
  • MPTP
  • Parkinson's disease
  • S100B

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    Sathe, K., Maetzler, W., Lang, J., Mounsey, R. B., Fleckenstein, C., Martin, H. L., Schulte, C., Mustafa, S., Synofzik, M., Vukovic, Z., Itohara, S., Berg, D., & Teismann, P. (2012). S100B is increased in Parkinson’s disease and ablation protects against MPTP-induced toxicity through the RAGE and TNF-α pathway. Brain, 135(11), 3336-3347. https://doi.org/10.1093/brain/aws250