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Mechanisms of Neurodegeneration and Axonal Dysfunction in Progressive Multiple Sclerosis

Department of Neurology, FLENI, Buenos Aires 1428, Argentina
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Biomedicines 2019, 7(1), 14; https://doi.org/10.3390/biomedicines7010014
Received: 29 January 2019 / Revised: 14 February 2019 / Accepted: 18 February 2019 / Published: 20 February 2019
(This article belongs to the Special Issue Multiple Sclerosis: Diagnosis and Treatment)
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Abstract

Multiple Sclerosis (MS) is a major cause of neurological disability, which increases predominantly during disease progression as a result of cortical and grey matter structures involvement. The gradual accumulation of disability characteristic of the disease seems to also result from a different set of mechanisms, including in particular immune reactions confined to the Central Nervous System such as: (a) B-cell dysregulation, (b) CD8+ T cells causing demyelination or axonal/neuronal damage, and (c) microglial cell activation associated with neuritic transection found in cortical demyelinating lesions. Other potential drivers of neurodegeneration are generation of oxygen and nitrogen reactive species, and mitochondrial damage, inducing impaired energy production, and intra-axonal accumulation of Ca2+, which in turn activates a variety of catabolic enzymes ultimately leading to progressive proteolytic degradation of cytoskeleton proteins. Loss of axon energy provided by oligodendrocytes determines further axonal degeneration and neuronal loss. Clearly, these different mechanisms are not mutually exclusive and could act in combination. Given the multifactorial pathophysiology of progressive MS, many potential therapeutic targets could be investigated in the future. This remains however, an objective that has yet to be undertaken. View Full-Text
Keywords: autoimmunity; axon; cortex; demyelination; mitochondria; multiple sclerosis; myelin; neurodegeneration; oligodendrocyte; progressive multiple sclerosis autoimmunity; axon; cortex; demyelination; mitochondria; multiple sclerosis; myelin; neurodegeneration; oligodendrocyte; progressive multiple sclerosis
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Correale, J.; Marrodan, M.; Ysrraelit, M.C. Mechanisms of Neurodegeneration and Axonal Dysfunction in Progressive Multiple Sclerosis. Biomedicines 2019, 7, 14.

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