Clemastine Confers Neuroprotection and Induces an Anti-Inflammatory Phenotype in SOD1(G93A) Mouse Model of Amyotrophic Lateral Sclerosis.

摘要: Mutations in the Cu(2+)/Zn(2+) superoxide dismutase 1 (SOD1) gene underlie 14-23 % of familial and 1-7 sporadic cases amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease characterized by specific loss motor neurons brain spinal cord. Neuroinflammation oxidative stress are emerging as key players pathogenesis ALS, thus justifying interest glial cells particularly microglia, addition to neurons, novel therapeutic approaches against ALS. Recently, histamine was proven participate neuroinflammatory diseases, particularly, microglia shown be sensitive challenge mainly through H1 receptors. Clemastine is first-generation CNS-penetrant receptor antagonist considered safe antihistamine compound that possess immune suppressive properties. In order investigate if clemastine might find promising application treatment this work, we tested its action SOD1(G93A) mouse model which extensively used ALS preclinical studies. We demonstrated chronic administration mice reduces microgliosis, modulates microglia-related inflammatory genes, enhances neuron survival. Moreover, vitro, able modify several activation parameters CD68 arginase-1 expression, well phospho-ERK1/2 NADPH oxidase 2 levels. Being drug already employed clinical practice, our results strongly encourage further exploitation candidate for trials new modulator neuroinflammation