Abstract:

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by coexisting processes of inflammation, demyelination, axonal neurodegeneration, and gliosis. Although autoimmune inflammation contributes to axonal pathology and demyelination, more recent evidence suggests that inflammation may also be beneficial. Protective autoimmunity is partly mediated via neurotrophic factors and neurotrophin regulation (Correale and Villa, 2004). Elevated neurotrophin levels have been observed during inflammatory processes, including in samples of in situ MS lesions, whole peripheral blood mononuclear cells (PBMC), serum, and cerebrospinal fluid (CSF) from MS patients. We recently demonstrated that T cells of MS patients could produce neurotrophins. The immune system may be modulated by neurotrophins and neurotrophin factors. The neurotrophins are a family of closely related proteins that were first identified as survival factors for sympathetic and sensory neurons and have since been shown to control a number of aspects of survival, development, and function of neurons in both the central and peripheral nervous systems. Neurotrophins belong to a class of growth factors and secreted proteins that are capable of signaling particular cells to survive, differentiate, and grow. Neurotrophins and neurotrophic factors might promote the survival of neurons by preventing programmed cell death, thereby allowing the neurons to survive. Neurotrophins can also induce differentiation of progenitor cellstoform neurons. Neurotrophins also act as neuroprotection mediators in CNS injury, indicating interactions between the immune cells and nervous systems. Neurotrophins are able to prevent neural death and favor the recovery process, neural regeneration, and remyelination. It has been shown that BDNF is one of the most potent factors supporting neuronal survival and regulating neurotransmitter release and dendritic growth in promoting the survival and differentiation of neurons. GDNF promotes axonal growth and induces remyelination. NGF promotes the biosynthesis of myelin by oligodendrocytes in CNS and by Schwann cells in the peripheral nervous system. It also promotes the differentiation of oligodendrocytes by cells of the subventricular zone in experimental autoimmune encephalomyelitis (EAE). Other studies have demonstrated the delayed onset of EAE by intra-cerebroventricular administration of NGF.