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.

Transgenerational modification of hippocampus TNF-α and S100B levels in the offspring of rats chronically exposed to morphine during adolescence

“…According to these studies, a close relationship exists between TNF-α and S100B levels in brain tissues, and typically, these levels are altered accordingly (22,55,56). In our study, the hippocampus TNF-α levels were increased while the S100B levels were inversely reduced as a result of chronic morphine exposure.…”

“…The S100B levels in hippocampus tissue and cerebrospinal fluid increase during brain damage or pathophysiological situations, and the consequent behavioral symptoms (28,30,(54)(55)(56)(57) might be induced by glial cell activation through the RAGE-dependent pathway (22,58). According to these studies, a close relationship exists between TNF-α and S100B levels in brain tissues, and typically, these levels are altered accordingly (22,55,56).…”

Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson's disease

“…High‐performance liquid chromatography (HPLC) with electrochemical detection was used to measure striatal levels of dopamine, and DOPAC using a method that has been described (Sathe et al, 2012). Briefly, mice were killed, 21 days after the last MPTP injection, and the striata were dissected out and snap frozen on solid carbon dioxide.…”

S100B-p53 disengagement by pentamidine promotes apoptosis and inhibits cellular migration via aquaporin-4 and metalloproteinase-2 inhibition in C6 glioma cells

“…S100B appears to be upregulated in numerous neurodegenerative diseases, including Alzheimer's and Parkinson's disease, and is known to be overexpressed in the majority of malignant gliomas (9)(10)(11). Furthermore, the S100B protein has been proposed to significantly contribute to cancer development by inhibiting the function of tumor suppressor protein p53 (12,13), and by stimulating the activity of the mitogenic kinases nuclear dbf2-related (14) and protein kinase B (15).…”