Title:Exploring the Role of Nerve Growth Factor in Multiple Sclerosis: Implications in Myelin Repair
Volume: 12
Issue: 8
Author(s): C.M.R. Acosta, C. Cortes, H. MacPhee and M.P. Namaka
Affiliation:
Keywords:
Cytokines, multiple sclerosis, myelin, nerve growth factor, neurotrophins, oligodendrocytes, re-myelination.
Abstract: Multiple sclerosis (MS) is a chronic disease resulting from targeted destruction of central nervous system
(CNS) myelin. MS is suggested to be an autoimmune disease involving the pathogenic activation of CD4+ T cells by a
foreign antigen in the peripheral blood. The activated CD4+ T cells liberate inflammatory cytokines that facilitate the
breakdown of the blood-brain barrier (BBB) promoting their passage into the CNS. Inside the CNS, CD4+ T cells
become re-activated by myelin proteins sharing a similar structure to the foreign antigen that initially triggered the
immune response. The CD4+ T cells continue to liberate inflammatory cytokines, such as tumor necrosis factor α
(TNFα), which activates macrophages and antibodies responsible for the phagocytosis of myelin. Acute CNS lesions can
be re-myelinated, however, the repair of chronic demyelinating lesions is limited, leading to permanent neurological
deficits. Although current MS treatments reduce severity and slow disease progression, they do not directly repair
damaged myelin. Henceforth, recent treatment strategies have focused on neurotrophins, such as nerve growth factor
(NGF) for myelin repair. NGF promotes axonal regeneration, survival, protection and differentiation of oligodendrocytes
(OGs) and facilitates migration and proliferation of oligodendrocyte precursors (OPs) to the sites of myelin damage.
NGF also directly regulates key structural proteins that comprise myelin. Interestingly, NGF also induces the production
of brain-derived neurotrophic factor (BDNF), another integral neurotrophin involved in myelination. The intricate
signaling between neurotrophins and cytokines that governs myelin repair supports the role of NGF as a leading
therapeutic candidate in white matter disorders, such as MS.
