Abstract
Multiple sclerosis (MS) is the most common autoimmune and demyelinating disease of the central nervous system (CNS), characterized, in the majority of cases, by initial relapses that later evolve into progressive neurodegeneration, severely impacting patients’ motor and cognitive functions. Despite the availability of immunomodulatory therapies effective to reduce relapse rate and slow disease progression, they all failed to restore CNS myelin that is necessary for MS full recovery. Microglia are the primary inflammatory cells present in MS lesions, therefore strongly contributing to demyelination and lesion extension. Thus, many microglial-based therapeutic strategies have been focused on the suppression of microglial pro-inflammatory phenotype and neurodegenerative state to reduce disease severity. On the other hand, the contribution of myelin phagocytosis advocating the neuroprotective role of microglia in MS has been less explored. Indeed, despite the presence of functional oligodendrocyte precursor cells (OPCs), within lesioned areas, MS plaques fail to remyelinate as a result of the over-accumulation of myelin-toxic debris that must be cleared away by microglia. Dysregulation of this process has been associated with the impaired neuronal recovery and deficient remyelination. In line with this, here we provide a comprehensive review of microglial myelin phagocytosis and its involvement in MS development and repair. Alongside, we discuss the potential of phagocytic-mediated therapeutic approaches and encourage their modulation as a novel and rational approach to ameliorate MS-associated pathology.
Highlights
Multiple sclerosis (MS) is the primary chronic autoimmune, demyelinating disease of the central nervous system (CNS), and the most debilitating condition in young adults aged between 20 and 45 years [1]
Liu et al observed that a new pharmacological treatment with pseudoginsenoside-F11 accelerated complement receptor 3 (CR3)-dependent myelin phagocytosis in a microglial culture after oxygen-glucose deprivation (OGD) and permanent middle cerebral artery occlusion in vivo and, by doing so, decreased de infarct area and improved neurological functions in pMCAO-treated rats [93]
Whereas as pro-inflammatory cells they contribute to disease burden, in an anti-inflammatory and regenerative state they are essential for disease recovery
Summary
Multiple sclerosis (MS) is the primary chronic autoimmune, demyelinating disease of the central nervous system (CNS), and the most debilitating condition in young adults aged between 20 and 45 years [1] It is mostly accepted, nowadays, that a dysregulation of the inflammatory response against myelin components-genetic and/or environmentally-mediated-leads to the recruitment of peripheral autoreactive T and B cells and macrophages across the blood-brain barrier (BBB). Due to their essential functions as immune mediators and primary phagocytes of the brain and spinal cord, microglia have attracted much attention and research This yolk sac-derived population colonizes the brain during embryogenesis and differentiates under the influence of CNS microenvironment [27], residing in the healthy nervous system as a highly stable population with long and ramified processes interacting with blood vessels, neurons, and other glial cells in a dynamic “surveillant state” [28]. Sci. 2020, 21, 5960 and targets with the potential to increase myelin clearance for disease amelioration but mostly for MS recovery
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