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Cited by 202Parkinson's Disease Mechanisms and TreatmentsS100 Proteins and AnnexinsNuclear Receptors and Signaling

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

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Sathe, Kinnari, Maetzler, Walter, Lang, Johannes D., Mounsey, Ross B., Fleckenstein, Corina, Martin, Heather L., Schulte, Claudia, Mustafa, Sarah +5 more·2012·Brain
DOI 10.1093/brain/aws250PMC PMC3501971
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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 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-α. 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.

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  • In vitro and in vivo studies revealed that silencing of HMGB1 or S100B reduced neuroinflammation and attenuated neurodegenerative diseases.

    “In vitro and in vivo studies revealed that silencing of HMGB1 or S100B reduced neuroinflammation and attenuated neurodegenerative diseases.336,337”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [337]

    The Results sections on MPTP toxicity and microgliosis report that S100B knockout mice had less neuronal loss and a reduced microglial response after MPTP treatment. The claim goes further than this source: its in vitro experiment blocked RAGE rather than silencing S100B, and it does not establish that silencing S100B attenuates neurodegenerative diseases generally. This verdict concerns the S100B portion of the sentence, not HMGB1, which may be covered by the other citation. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Deficiency of RAGE improved the survival of dopaminergic neurons in an MPTP-induced PD mouse model.

    “Deficiency of RAGE improved the survival of dopaminergic neurons in an MPTP-induced PD mouse model.337,340”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [337]

    The Discussion (page not available) reports that RAGE ablation had a neuroprotective effect in an MPTP model of Parkinson’s disease. It does not specify improved dopaminergic-neuron survival for RAGE-deficient mice; the Results report that outcome for S100B-deficient mice instead. (LLM, conf=0.83)

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Authors
Sathe, K., Maetzler, W., Lang, J. D., Mounsey, R. B., Fleckenstein, C., Martin, H. L., Schulte, C., Mustafa, S., Synofzik, M., Vukovic, Z., Itohara, S., Berg, D., & Teismann, P.
Affiliations
  • University of Aberdeen (GB)
  • Hertie Institute for Clinical Brain Research (DE)
  • RIKEN Center for Brain Science (JP)
Corresponding author
  • Sathe, Kinnari
  • Teismann, Peter
ORCID
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2012-11
Volume
135
Issue
11
Pages
3336-3347
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/aws250
PMC
PMC3501971
OpenAlex
W2102816531
Cited by
202
References
3
Citations by year
2026: 6 · 2025: 22 · 2024: 14 · 2023: 23 · 2022: 18 · 2021: 11 · 2020: 19 · 2019: 9 · 2018: 13 · 2017: 18 · 2016: 10 · 2015: 22 · 2014: 9 · 2013: 8
FWCI
8.15
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Brain (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
  • DZNE Pub (submittedVersion)
Funders
  • Parkinson's Disease Foundation
  • Wellcome Trust (WT080782MF)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
S100B, Parkinson's disease, MPTP-induced neurotoxicity, RAGE, TNF-α, neuroprotection, microglial activation, substantia nigra, cerebrospinal fluid biomarkers, astrocytes, neuroinflammation, neurodegeneration
MeSH terms
Receptor for Advanced Glycation End Products, Aged, Animals, Cell Line, Disease Models, Animal, Female, Gliosis, Humans, Male, Mice, Inbred C57BL, Nerve Growth Factors, S100 Proteins, Parkinson Disease, Receptors, Immunologic, Substantia Nigra, Tumor Necrosis Factor-alpha, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Up-Regulation, Case-Control Studies, Mice, Knockout, Neuroprotective Agents, Mice, S100 Calcium Binding Protein beta Subunit

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