The Antiaging Protein Klotho Enhances Oligodendrocyte Maturation and Myelination of the CNS

摘要: We have previously shown that myelin abnormalities characterize the normal aging process of brain and an age-associated reduction in Klotho is conserved across species. Predominantly generated kidney, overexpression extends life span, whereas loss accelerates development aging-like phenotypes. Although function unknown, expression leads to cognitive deficits. found significant effects on oligodendrocyte functions, including induced maturation rat primary oligodendrocytic progenitor cells (OPCs) vitro myelination. Phosphoprotein analysis indicated Klotho's downstream involve Akt ERK signal pathways. increased OPC maturation, inhibition or blocked this effect OPCs. In vivo studies knock-out mice control littermates revealed a major protein gene expression. By immunohistochemistry, number total mature oligodendrocytes was significantly lower mice. Strikingly, at ultrastructural level, exhibited impaired myelination optic nerve corpus callosum. These also displayed severe nodes Ranvier. To decipher mechanisms by which affects oligodendrocytes, we used luciferase pathway reporters identify transcription factors involved. Together, these provide novel evidence for as key player biology, may thus be useful therapeutic target efforts protect against age-dependent changes promote repair multiple sclerosis.