The Role of Neurotrophins in Multiple Sclerosis—Pathological and Clinical Implications

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.

Multiple sclerosis-induced neuropathic pain: pharmacological management and pathophysiological insights from rodent EAE models

“…Although neurotrophins also regulate neuronal growth and myelination in the CNS (Kalinowska-Lyszczarz and Losy 2012), it is unclear whether they have a protective or detrimental effect in MS-associated neuropathic pain. In a demyelinating EAE-rat model of MS, altered thermal nociception and motor deficits were improved by chronic treatment with the adrenocorticotrophic hormone analogue, [ACTH] 4–9 , suggesting that neurotrophic therapy may have benefit for relief of MS-associated neuropathic pain (Duckers et al 1996).…”

Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis

“…Neurotrophins such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) reciprocally promote angiogenesis [111,112], and higher amounts of both have been detected in CSF from MS patients [113,114]. BDNF and its receptor tyrosine kinase (gp145trkB) have been involved in immune-mediated neuroprotection in MS lesions [115,116]. In other situations, vessels act as guidance templates for axons, releasing guidance cues such as VEGF, artemin, neurotrophin-3 or ET-3 [117].…”

Reaction of food‐specific antibodies with different tissue antigens

“…However, immune reaction between anti‐corn antibody and ten out of sixty‐five tested tissue antigens, as shown in Fig. , indicates that immune reaction by these tissue antigens with corn proteins may play a role in additional autoimmunities, such as intrinsic factor in pernicious anaemia, thyroid peroxidase (TPO) in thyroid autoimmunity, alpha‐myosin in cardiovascular autoimmunity, tyrosinase in autoimmune vitiligo, and neurotrophin in MS, alopecia areata and Alzheimer’s disease (Botchkarev, ; Ongenae et al , ; Lv et al , ; Andres & Serraj, ; Kalinowska‐Lyszczarz & Losy, ; Fröhlich & Wahl, ; Vojdani et al , ). With regard to reactivity between anti‐soy antibody and different tissue antigens, the reaction was strongest with tyrosinase, intrinsic factor and alpha‐enolase, which are known to be involved in pernicious anaemia, vitiligo and rheumatoid arthritis (RA) (Ongenae et al , ; Lundberg et al , ; Andres & Serraj, ).…”