Activation of endogenous neural stem cells for multiple sclerosis therapy

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic neurological disability. A promising perspective for future therapy of MS is the regeneration of lesions with replacement of the damaged oligodendrocytes or neurons. Therapies targeting to the enhancement of endogenous remyelination, aim to promote the activation of either the parenchymal oligodendrocyte progenitor cells or the subventricular zone-derived neural stem cells (NSCs). Less studied but highly potent, is the strategy of neuronal regeneration with endogenous NSCs that although being linked to numerous limitations, is anticipated to ameliorate cognitive disability in MS. Focusing on the forebrain, this review highlights the role of NSCs in the regeneration of MS lesions.

Keywords: gliogenesis; multiple sclerosis; neural stem cells; neurogenesis; therapy.

Figure 1

Model strategy for regeneration of MS lesions via activation of adult SVZ-derived NSCs. Stimulation of neural stem cells (NSCs) via intracerebroventricular administration of, e.g., growth factors may lead to the regeneration of newly formed lesions which are located in white matter (WM) or gray matter (GM) areas nearby the subventricular zone (SVZ) of the multiple sclerosis (MS) brain (A) such as the adjacent corpus callosum (CC) (B) and the cingulate gyrus (C).