The S100B Inhibitor Pentamidine Ameliorates Clinical Score and Neuropathology of Relapsing-Remitting Multiple Sclerosis Mouse Model.

Publication date: Mar 18, 2020

S100B is an astrocytic protein acting either as an intracellular regulator or an extracellular signaling molecule. A direct correlation between increased amount of S100B and demyelination and inflammatory processes has been demonstrated. The aim of this study is to investigate the possible role of a small molecule able to bind and inhibit S100B, pentamidine, in the modulation of disease progression in the relapsing-remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the central nervous system, we observed that pentamidine is able to delay the acute phase of the disease and to inhibit remission, resulting in an amelioration of clinical score when compared with untreated relapsing-remitting experimental autoimmune encephalomyelitis mice. Moreover, we observed a significant reduction of proinflammatory cytokines expression levels in the brains of treated versus untreated mice, in addition to a reduction of nitric oxide synthase activity. Immunohistochemistry confirmed that the inhibition of S100B was able to modify the neuropathology of the disease, reducing immune infiltrates and partially protecting the brain from the damage. Overall, our results indicate that pentamidine targeting the S100B protein is a novel potential drug to be considered for multiple sclerosis treatment.

Open Access PDF

Di Sante, G., Amadio, S., Sampaolese, B., Clementi, M.E., Valentini, M., Volont’e, C., Casalbore, P., Ria, F., and Michetti, F. The S100B Inhibitor Pentamidine Ameliorates Clinical Score and Neuropathology of Relapsing-Remitting Multiple Sclerosis Mouse Model. 20510. 2020 Cells (9):3.

Concepts Keywords
Astrocytic Experimental autoimmune encephalomyelitis
Brain Damage Relapsing–remitting
Central Nervous System S100B
Correlation Branches of biology
Cytokines Molecular neuroscience
Demyelination Nervous system
Extracellular Organ systems
Immunohistochemistry Multiple sclerosis
Intracellular Neuropathology disease
Mice Multiple sclerosis treatment
Multiple Sclerosis
Nitric Oxide Synthase
Signaling Molecule
Small Molecule


Type Source Name
drug DRUGBANK Pentamidine
disease MESH Relapsing-Remitting Multiple Sclerosis
disease MESH demyelination
disease MESH disease progression
disease MESH experimental autoimmune encephalomyelitis
disease MESH multiple sclerosis
disease MESH Pathology
disease MESH sclerosis
disease MESH inflammation
disease MESH gliosis
disease MESH oxidative stress
disease MESH amyotrophic lateral sclerosis 5
disease MESH relapse
disease MESH death
disease MESH suffering
drug DRUGBANK Ketamine
drug DRUGBANK Xylazine
drug DRUGBANK Nitric Oxide
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Oxygen
drug DRUGBANK Nitrate
drug DRUGBANK Nitrite
drug DRUGBANK Sucrose
drug DRUGBANK Biotin
drug DRUGBANK Abacavir
drug DRUGBANK Pentaerythritol tetranitrate
disease MESH encephalomyelitis
drug DRUGBANK Acetylcholine
drug DRUGBANK L-Arginine
pathway KEGG Apoptosis
disease MESH pus
disease MESH paralysis
disease MESH sepsis associated encephalopathy
drug DRUGBANK Coenzyme M
disease MESH arthritis
pathway KEGG Autophagy
disease MESH Point Mutation
disease MESH malignant melanoma
drug DRUGBANK Isoxaflutole
drug DRUGBANK Pyridoxal Phosphate
disease MESH tuberculosis
pathway KEGG Tuberculosis
drug DRUGBANK Guanosine
disease MESH Aging
disease MESH pneumonia
disease MESH Pneumocystis carinii pneumonia
drug DRUGBANK Fluorouracil
disease MESH Mucositis
disease MESH malignancy
disease MESH Mult
disease MESH colitis
disease MESH Rheumatoid arthritis
pathway KEGG Rheumatoid arthritis
disease MESH infection


Original Article

Leave a Comment

Your email address will not be published. Required fields are marked *