The role of neurotrophins in multiple sclerosis-pathological and clinical implications

Int J Mol Sci. 2012 Oct 22;13(10):13713-25. doi: 10.3390/ijms131013713.

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.

Publication types

  • Review

MeSH terms

  • Autoimmunity
  • Blood-Brain Barrier / metabolism
  • CD40 Ligand / metabolism
  • Central Nervous System / metabolism
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / pathology*
  • Nerve Growth Factors / metabolism*
  • Neuroprotective Agents / therapeutic use
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Nerve Growth Factors
  • Neuroprotective Agents
  • CD40 Ligand