Multiple sclerosis-remyelination failure as a cause of disease progression

K Hagemeier, W Brück, T Kuhlmann - 2012 - digitum.um.es
K Hagemeier, W Brück, T Kuhlmann
2012digitum.um.es
Multiple sclerosis (MS) is the most frequent demyelinating disease of the central nervous
system (CNS) that affects worldwide about 2.5 million people. The morphological correlates
of the disease are multiple lesions in brain and spinal cord which are characterized by
demyelination, inflammation, gliosis and axonal damage. The underlying cause for the
permanent neurological deficits in MS patients is axonal loss. Demyelinated axons are
prone to damage due to the lack of trophic support by myelin sheaths and oligodendrocytes …
Multiple sclerosis (MS) is the most frequent demyelinating disease of the central nervous system (CNS) that affects worldwide about 2.5 million people. The morphological correlates of the disease are multiple lesions in brain and spinal cord which are characterized by demyelination, inflammation, gliosis and axonal damage. The underlying cause for the permanent neurological deficits in MS patients is axonal loss. Demyelinated axons are prone to damage due to the lack of trophic support by myelin sheaths and oligodendrocytes, as well as the increased vulnerability to immune mediated attacks. Remyelination occurs, but especially in chronic lesions is frequently limited to a small rim at the lesion border. Current treatment strategies are based on anti-inflammatory or immunomodulatory drugs and have the potential to reduce the numbers of newly evolving lesions, although as yet no treatment strategy exists to influence or prevent the progressive disease phase. Therefore, the development of neuroprotective treatment options, such as the promotion of endogenous remyelination is an attractive strategy. A prerequisite for the development of such new treatments is the understanding of the mechanisms leading to remyelination and the reasons for insufficient endogenous repair in chronic MS. This review will therefore provide an overview of the current concepts regarding remyelination in the rodent and human CNS. We will also summarize a selected number of inhibitory pathways and non-disease related factors which may contribute to remyelination failure in chronic MS.
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