title: S100B is increased in Parkinson's disease and ablation protects against MPTP-induced toxicity through the RAGE and TNF-α 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-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.
authors.affiliation: School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Kinnari
authors.initials: K
authors.lastname: Sathe
authors.forename: Walter
authors.initials: W
authors.lastname: Maetzler
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Lang
authors.forename: Ross B
authors.initials: RB
authors.lastname: Mounsey
authors.forename: Corina
authors.initials: C
authors.lastname: Fleckenstein
authors.forename: Heather L
authors.initials: HL
authors.lastname: Martin
authors.forename: Claudia
authors.initials: C
authors.lastname: Schulte
authors.forename: Sarah
authors.initials: S
authors.lastname: Mustafa
authors.forename: Matthis
authors.initials: M
authors.lastname: Synofzik
authors.forename: Zvonimir
authors.initials: Z
authors.lastname: Vukovic
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
authors.forename: Peter
authors.initials: P
authors.lastname: Teismann
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors; D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D010300:Parkinson Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C579159:S100b protein, mouse; D014409:Tumor Necrosis Factor-alpha; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine