Category: Parkinson's Disease: Pathophysiology
Objective: This review aims to analyze studies on the implication of S100B in Parkinson’s Disease (PD) and shed light on Pentamidine as a novel treatment in the field of disease therapeutics.
Background: PD is characterized by a loss of dopaminergic neurons and the accumulation of α-synuclein in neurons in the brainstem and cortical regions . Evidence has shown increased levels of S100B – a calcium-binding protein secreted by astrocytes- contributes to the pathogenesis of PD, mainly by regulating neuroinflammation and dopamine metabolism. Pentamidine, is an antiprotozoal drug that directly blocks S100B activity .
Method: A literature search was conducted on PubMed and Google Scholar databases for English, peer-reviewed articles and reviews published between January 2000-January 2021. Search terms were: “neuroinflammation AND Parkinson’s disease”, “S100B AND Parkinson’s disease”, “Pentamidine AND S100B”. Case reports were excluded. Focus was placed on animal- or human-based studies.
Results: S100B has shown to contribute to neurodegeneration in animal models of PD. In vitro studies revealed that elevated S100B was associated with increased glial cell proliferation and reduced neuronal survival . Other experimental studies showed S100B overexpression in transgenic mice caused motor deficits through inhibition of dopamine D2 receptor expression and promotion of oxidative stress with secretion of pro-inflammatory cytokines . Moreover, S100B promoted the proinflammatory M1 phenotype microglia and inhibited the anti‑inflammatory M2 phenotype causing cerebral ischemia . In post-mortem human studies, S100B levels were increased in the substantia nigra and the dorsomedial prefrontal cortex of patients with PD compared to those without PD  Clinically, elevated serum S100B levels resulted in increased disease severity with respects to motor symptoms in PD patients . However, Pentamadine, a S100B inhibitor, has shown to ameliorate motor deficits in transgenic mice . In addition, studies have revealed the drug has prevented dopaminergic neuronal loss and neuroinflammation in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treated mice.
Conclusion: Emerging evidence suggests S100B mediates the pathogenesis of PD and is a potential therapeutic target against the disease. Therefore, Pentamdine, a S100B inhibitor seems promising in the treatment of PD. Limitations, implications, and future directions for research are discussed.
References: 1) Sathe K et al (2012) S100B is increased in Parkinson’s disease and ablation protects against MPTP-induced toxicity through the RAGE and TNF-alpha pathway. Brain 135(Pt 11):3336–3347 2) Di Sante, G., Amadio, S., Sampaolese, B., Clementi, M. E., Valentini, M., Volonté, C., Casalbore, P., Ria, F., & Michetti, F. (2020). The S100B Inhibitor Pentamidine Ameliorates Clinical Score and Neuropathology of Relapsing-Remitting Multiple Sclerosis Mouse Model. Cells, 9(3), 748. https://doi.org/10.3390/cells9030748 3) Brozzi, F., Arcuri, C., Giambanco, I., & Donato, R. (2009). S100B Protein Regulates Astrocyte Shape and Migration via Interaction with Src Kinase: IMPLICATIONS FOR ASTROCYTE DEVELOPMENT, ACTIVATION, AND TUMOR GROWTH. The Journal of biological chemistry, 284(13), 8797–8811. https://doi.org/10.1074/jbc.M805897200 4) Businaro R et al (2006) S100B protects LAN-5 neuroblastoma cells against Abeta amyloid-induced neurotoxicity via RAGE engagement at low doses but increases Abeta amyloid neurotoxicity at high doses. J Neurosci Res 83(5):897–906 5) Zhou S et al (2018) S100B promotes microglia M1 polarization and migration to aggravate cerebral ischemia. Inflamm Res 67(11–12):937–949 6) Cunha MP et al (2017) MPP(+)-lesioned mice: an experimental model of motor, emotional, memory/learning, and striatal neurochemical dysfunctions. Mol Neurobiol 54(8):6356–6377. 7) Rinaldi F et al (2019) inPentasomes: An innovative nose-to-brain pentamidine delivery blunts MPTP parkinsonism in mice. J Control Release 294:17–26
To cite this abstract in AMA style:V. Balendra. Role of S100B in the Pathogenesis of Parkinson’s Disease [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/role-of-s100b-in-the-pathogenesis-of-parkinsons-disease/. Accessed December 7, 2023.
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