Abstract
Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) with unknown etiology. It was recently suggested that autoimmunity, which had long been considered to be destructive in MS, might also play a protective role in the CNS of MS patients. Neurotrophins are polypeptides belonging to the neurotrophic factor family. While neurotrophins mediate cell survival and proliferation in the nervous system, they are also expressed within peripheral blood mononuclear cells fraction (PBMCs) of immunological system. In MS additional neurotrophic support from PBMCs might compensate relative neurotrophins deficiency in the damaged CNS tissue that needs to be repaired. Failure to produce the adequate neurotrophins concentrations might result in decreased protection of the CNS, consequently leading to increased atrophy, which is the main determinant of MS patients’ end-point disability. There are several lines of evidence, both from clinical research and animal models, suggesting that neurotrophins play a pivotal role in neuroprotective and neuroregenerative processes that are often defective in the course of MS. It seems that neuroprotective strategies might be used as potentially valuable add-on therapies, alongside traditional immunomodulatory treatment in multiple sclerosis.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), with yet unknown etiology, leading to formation of disseminated demyelinating lesions and accompanied by axonal degeneration
In the healthy adult CNS neurons are the main source of neurotrophins and the role of immune cell-derived neurotrophic factors is most probably marginal, especially since it is only the activated immunological cells that can cross the blood-brain barrier and they do not get activated in the undamaged brain
It seems crucial to identify the mechanism in which peripheral blood mononuclear cells (PBMCs) are stimulated to produce neurotrophins and release them into the plaque area
Summary
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS), with yet unknown etiology, leading to formation of disseminated demyelinating lesions and accompanied by axonal degeneration. Several therapies are currently approved for MS treatment, and a considerate number is still under clinical trials. Their primary effect is the reduction of the annual relapse rate and of the radiological activity of the disease, as described by the number of new gadolinium-enhancing lesions and new T2-hyperintense lesions demonstrated in subsequent magnetic resonance imaging (MRI). In the recent years attention has been drawn to its neurodegenerative aspect. In this context studies on the potentially protective role of neurotrophic factors have emerged in MS research. In this review the role of neurotrophins in multiple sclerosis is presented and potential future therapeutic options are discussed
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