Growing role of S100B protein as a putative therapeutic target for neurological- and nonneurological-disorders

Michetti, Fabrizio; Sante, Gabriele Di; Clementi, Maria Elisabetta; Sampaolese, Beatrice; Casalbore, Patrizia; Volonté, Cinzia; Spica, Vincenzo Romano; Parnigotto, Pier Paolo; Liddo, Rosa Di; Amadio, Susanna; Ria, Francesco

doi:10.1016/j.neubiorev.2021.04.035

Cited by 28 publications

(38 citation statements)

References 259 publications

(272 reference statements)

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“…This extended PPI network of S100B protein enables regulation of numerous vital processes, such as cell proliferation, differentiation and locomotion, cytoskeleton organization, Ca 2+ homeostasis, protein degradation and phosphorylation, receptors, enzymes and transcription factors [36]. S100B is associated with multiple sclerosis, cancer, SARS-CoV-2, acute neural injury, Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, schizophrenia, epilepsy, bipolar disorder, depression, obesity, diabetes, inflammatory bowel disease, psoriasis, muscular dystrophy, and uveal and retinal disorders [39][40][41][42][43][44]. S100B is clinically used for diagnostics of melanoma, breast cancer, and brain injury [45].…”

Section: Introductionmentioning

confidence: 99%

Interferon-β Activity Is Affected by S100B Protein

Kazakov

Sofin

Avkhacheva

et al. 2022

IJMS

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Interferon-β (IFN-β) is a pleiotropic cytokine secreted in response to various pathological conditions and is clinically used for therapy of multiple sclerosis. Its application for treatment of cancer, infections and pulmonary diseases is limited by incomplete understanding of regulatory mechanisms of its functioning. Recently, we reported that IFN-β activity is affected by interactions with S100A1, S100A4, S100A6, and S100P proteins, which are members of the S100 protein family of multifunctional Ca2+-binding proteins possessing cytokine-like activities (Int J Mol Sci. 2020;21(24):9473). Here we show that IFN-β interacts with one more representative of the S100 protein family, the S100B protein, involved in numerous oncological and neurological diseases. The use of chemical crosslinking, intrinsic fluorescence, and surface plasmon resonance spectroscopy revealed IFN-β binding to Ca2+-loaded dimeric and monomeric forms of the S100B protein. Calcium depletion blocks the S100B–IFN-β interaction. S100B monomerization increases its affinity to IFN-β by 2.7 orders of magnitude (equilibrium dissociation constant of the complex reaches 47 pM). Crystal violet assay demonstrated that combined application of IFN-β and S100B (5–25 nM) eliminates their inhibitory effects on MCF-7 cell viability. Bioinformatics analysis showed that the direct modulation of IFN-β activity by the S100B protein described here could be relevant to progression of multiple oncological and neurological diseases.

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Section: Introductionmentioning

confidence: 99%

Interferon-β Activity Is Affected by S100B Protein

Kazakov

Sofin

Avkhacheva

et al. 2022

IJMS

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“…S100b is overexpressed in both AD patients and AD models, especially in the severely affected regions of the brain. 38 , 39 Fabp7 is a newly found gene, which is involved in the proliferation of reactive astrocytes. 40 Both S100b and Fabp7 are part of the proliferation and activation of astrocytes.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Bioactivity Evaluation of a Novel 1,2,4-Oxadiazole Derivative in vitro and in 3×Tg Mice

Luo¹,

Wang²,

Pang³

et al. 2022

DDDT

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Aim Alzheimer’s disease (AD) is the most common neurodegenerative disease whose patients suffered from cognitive impairments. In our study, a novel 1,2,4-Oxadiazole derivative wyc-7-20 was synthesized, which showed low cytotoxicity and potent neuroprotective effect at the cellular level. Improved cognitive impairments, β-amyloid (Aβ) clearance, and tau pathological phenotypes were detected in transgenic animal models after wyc-7-20 treatment. Reversed expressions in AD-related genes were also detected. The results demonstrated wyc-7-20 was potent in AD therapy. Purpose The pathological complexity of AD increased difficulties in medical research. To explore a new potential medical treatment for AD, a novel 1,2,4-Oxadiazole derivative (wyc-7-20) was designed, synthesized to explore the application in this study. Materials and Methods Human neuroblastoma (SH-SY5Y) cells and human hepatocellular carcinoma (HepG2) cells were used to detect median lethal dose (LD50). H 2 O 2 and Aβ 1–42 oligomers (AβOs) were respectively, added into SH-SY5Y cells to detect anti-ROS (reactive oxygen species) and anti-AβOs effects of wyc-7-20. 3×Tg mice were administered with wyc-7-20, and then Y maze test and Morris water maze (MWM) test were applied to detect cognitive improvements. Brain tissue samples were subsequently collected and analyzed using different techniques. Results wyc-7-20 showed low cytotoxicity and potent neuroprotective effect at the cellular level. Improved cognitive impairments, Aβ clearance, and tau pathological phenotypes were detected in transgenic animal models after wyc-7-20 treatment. Reversed expressions in AD-related genes were also detected. Conclusion wyc-7-20 was potent in AD therapy.

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“…Thus, these results pave a way to promising research addressing possible pathways connecting AA, PTM, S100B, and immunomodulation. In any case, clinical trials for the use of the AA to counteract other neural disorders, such as acute brain injury, amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease, have already been performed [40], and interestingly, S100B is regarded to play a crucial role in pathogenic processes of all previously cited disorders [5]. This study reinforces the involvement of S100B in MS processes after our first demonstration in vivo that interference with S100B activity ameliorates RR-EAE [13] and is a prerequisite step towards clinical trials addressing the use of AA in MS.…”

Section: Discussionmentioning

confidence: 99%

“…Data have been reported, indicating S100B as a key molecule in pathogenic processes and S100B levels in biological fluids as a reliable biomarker in a series of neural disorders, including acute brain injury, Alzheimer's disease, Parkinson's disease, or amyotrophic lateral sclerosis. Interestingly, in many cases, data have shown that the overexpression/administration of the protein induces the worsening of the disease, while its deletion/inactivation produces the amelioration of these disorders [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

S100B Protein as a Therapeutic Target in Multiple Sclerosis: The S100B Inhibitor Arundic Acid Protects from Chronic Experimental Autoimmune Encephalomyelitis

Camponeschi

Carluccio

Amadio

et al. 2021

IJMS

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S100B is an astrocytic protein behaving at high concentration as a damage-associated molecular pattern molecule. A direct correlation between the increased amount of S100B and inflammatory processes has been demonstrated, and in particular, the inhibitor of S100B activity pentamidine has been shown to ameliorate clinical scores and neuropathologic-biomolecular parameters in the relapsing-remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. This study investigates the effect of arundic acid (AA), a known inhibitor of astrocytic S100B synthesis, in the chronic experimental autoimmune encephalomyelitis, which is another mouse model of multiple sclerosis usually studied. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the spinal cord, we observed that the AA-treated group showed lower severity compared to the vehicle-treated mice, particularly in the early phase of disease onset. We also observed a significant reduction of astrocytosis, demyelination, immune infiltrates, proinflammatory cytokines expression and enzymatic oxidative reactivity in the AA-treated group. Overall, our results reinforce the involvement of S100B in the development of animal models of multiple sclerosis and propose AA targeting the S100B protein as a focused potential drug to be considered for multiple sclerosis treatment.

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Growing role of S100B protein as a putative therapeutic target for neurological- and nonneurological-disorders

Cited by 28 publications

References 259 publications

Interferon-β Activity Is Affected by S100B Protein

Interferon-β Activity Is Affected by S100B Protein

Synthesis and Bioactivity Evaluation of a Novel 1,2,4-Oxadiazole Derivative in vitro and in 3×Tg Mice

S100B Protein as a Therapeutic Target in Multiple Sclerosis: The S100B Inhibitor Arundic Acid Protects from Chronic Experimental Autoimmune Encephalomyelitis

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