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

doi:10.1093/brain/aws250

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

Medical Sciences

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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 language	English
Pages (from-to)	3336-3347
Number of pages	12
Journal	Brain
Volume	135
Issue number	11
DOIs	https://doi.org/10.1093/brain/aws250
Publication status	Published - Nov 2012

Keywords

calcium-binding protein
MPTP
Parkinson's disease
S100B

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10.1093/brain/aws250

2012 Sathe S100B Brain
Sathe, K, Maetzler, W, Lang, J, Mounsey, RB, Fleckenstein, C, Martin, HL, 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-a pathway' Brain, vol 135, no. 11, pp. 3336-3347. Copyright © 2013 Oxford University Press DOI: 10.1093/brain/aws250
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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

Sathe, K, Maetzler, W, Lang, J, Mounsey, RB, Fleckenstein, C, Martin, HL, 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, vol. 135, no. 11, pp. 3336-3347. https://doi.org/10.1093/brain/aws250

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title = "S100B is increased in Parkinson{\textquoteright}s disease and ablation protects against MPTP-induced toxicity through the RAGE and TNF-α pathway",

abstract = "Parkinson{\textquoteright}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 is25 increasing evidence that S100B acts as a cytokine or damage-associated molecular pattern protein not only in inflammatorybut also in neurodegenerative diseases. In this study, we show that S100B protein levels were higher in post-mortem substantianigra of patients with Parkinson{\textquoteright}s disease compared with control tissue, and CSF S100B levels were higher in a large cohort ofpatients with Parkinson{\textquoteright}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 in30 neuroprotection, reduced microgliosis and reduced expression of both the receptor for advanced glycation endproducts andtumour necrosis factor-a. Our results demonstrate a role of S100B in the pathophysiology of Parkinson{\textquoteright}s disease. TargetingS100B may emerge as a potential treatment strategy in this disorder.",

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

year = "2012",

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T1 - S100B is increased in Parkinson’s disease and ablation protects against MPTP-induced toxicity through the RAGE and TNF-α pathway

AU - Sathe, Kinnari

AU - Maetzler, Walter

AU - Lang, Johannes

AU - Mounsey, Ross Brian

AU - Fleckenstein, Corinna

AU - Martin, Heather Louise

AU - Schulte, Claudia

AU - Mustafa, Sarah

AU - Synofzik, Matthis

AU - Vukovic, Zvonimir

AU - Itohara, Shigeyoshi

AU - Berg, Daniela

AU - Teismann, Peter

PY - 2012/11

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N2 - 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 is25 increasing evidence that S100B acts as a cytokine or damage-associated molecular pattern protein not only in inflammatorybut also in neurodegenerative diseases. In this study, we show that S100B protein levels were higher in post-mortem substantianigra of patients with Parkinson’s disease compared with control tissue, and CSF S100B levels were higher in a large cohort ofpatients 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 in30 neuroprotection, reduced microgliosis and reduced expression of both the receptor for advanced glycation endproducts andtumour necrosis factor-a. Our results demonstrate a role of S100B in the pathophysiology of Parkinson’s disease. TargetingS100B may emerge as a potential treatment strategy in this disorder.

AB - 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 is25 increasing evidence that S100B acts as a cytokine or damage-associated molecular pattern protein not only in inflammatorybut also in neurodegenerative diseases. In this study, we show that S100B protein levels were higher in post-mortem substantianigra of patients with Parkinson’s disease compared with control tissue, and CSF S100B levels were higher in a large cohort ofpatients 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 in30 neuroprotection, reduced microgliosis and reduced expression of both the receptor for advanced glycation endproducts andtumour necrosis factor-a. Our results demonstrate a role of S100B in the pathophysiology of Parkinson’s disease. TargetingS100B may emerge as a potential treatment strategy in this disorder.

KW - calcium-binding protein

KW - MPTP

KW - Parkinson's disease

KW - S100B

U2 - 10.1093/brain/aws250

DO - 10.1093/brain/aws250

M3 - Article

SN - 0006-8950

VL - 135

SP - 3336

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JO - Brain

JF - Brain

IS - 11

ER -

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

Abstract

Keywords

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