Neurotrophic cross‐talk between the nervous and immune systems: Implications for neurological diseases

Abstract

Inflammatory reactions in the central nervous system usually are considered detrimental, but recent evidence suggests that they also can be beneficial and even have neuroprotective effects. Intriguingly, immune cells can produce various neurotrophic factors of various molecular families. The concept of "neuroprotective immunity" will have profound consequences for the pathogenesis and treatment of neuroinflammatory diseases such as multiple sclerosis. It also will prove important for neurodegenerative disorders, in which inflammatory reactions often occur. This review focuses on recent findings that immune cells produce brain-derived neurotrophic factor in multiple sclerosis lesions, whereas neurons and astrocytes express the appropriate tyrosine kinase receptor TrkB. Together with functional evidence for the neuroprotective effects of immune cells, these observations support the concept of "neuroprotective immunity." We next examine current and future therapeutic strategies for multiple sclerosis and experimental autoimmune encephalomyelitis in light of neuroprotective immunity and finally address the broader implications of this new concept for other neuroinflammatory and neurodegenerative diseases.

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

“…Experimental data show that receptor selectivity, time frame and concentration of hormone, as well as cell-specific molecular partners are key features in the efficacy of estrogens to control microglia and brain inflammation. It is worth underscoring that microglia activation associated with neurodegenerative processes is also endowed with beneficial effects, as microglia cells were shown to produce trophic and survival factors and to eliminate through phagocytosis the noxious material accumulated in the extracellular space ( [118,147]). Identifying the molecular mechanisms of estrogen action will elucidate the conditions regulating the beneficial vs detrimental pathways can be separately activated, leading to the design of more selective regulatory agents that inhibit the deleterious effects while maintaining the protective role played by these immune cells in the neural tissue.…”

Targeting Experimental Autoimmune Encephalomyelitis Lesions to a Predetermined Axonal Tract System Allows for Refined Behavioral Testing in an Animal Model of Multiple Sclerosis

“…Growth factors, eg, of the families of neurotrophic factors, have shown considerable potential as therapeutic agents for MS. 47,56,57 Their particular appeal resides in the pleiotrophy inheritant to their actions, which comprise the protection of axons and myelin, stimulation of axonal regeneration, as well as immunomodulatory properties. 58,59 The development of repair strategies aiming at both the replacement of damaged glial cells and the functional reconnection of interrupted axonal connections are further exciting perspectives for future research. 9,60 Cell transplantation approaches are obviously facilitated in a localized EAE model with a predetermined localization of the lesion.…”

Mechanism of Action of Glatiramer Acetate in Treatment of Multiple Sclerosis

“…17,18 BDNF is an important factor for differentiation and survival of neurons and is required for maintenance of various glial cell functions. 59 Although the ability to produce BDNF is unlikely to be restricted to GA-reactive T cells, it may relate to the activation status of immune cells (e.g., T cells). 60 In this regard, the continuous activation by daily GA application may promote BDNF production of GAreactive T cells in vivo.…”