The molecular basis of neurodegeneration in multiple sclerosis

Abstract

a b s t r a c tStudies aimed to elucidate the pathogenesis of the disease and to find new therapeutic options for multiple sclerosis (MS) patients heavily rely on experimental autoimmune encephalomyelitis (EAE) as a suitable experimental model. This strategy has been highly successful for the inflammatory component of the disease, but had so far little success in the development of neuroprotective therapies, which are also effective in the progressive stage of the disease. Here we discuss opportunities and limitations of EAE models for MS research and provide an overview on the complex mechanisms leading to demyelination and neurodegeneration in this disease. We suggest that the underlying mechanisms involve adaptive and innate immunity. However, mitochondrial injury, resulting in energy failure, is a key element of neurodegeneration in MS and is apparently driven by radical production in activated microglia.

Effect of Fingolimod on Neural Stem Cells: A Novel Mechanism and Broadened Application for Neural Repair

“…1,2 It is believed that at the chronic stage of MS and of its animal model, experimental autoimmune encephalomyelitis (EAE), the main processes underlying disease progression are OLG and neuron death, axonal loss, and myelin destruction. 3,4 In the last few decades, immunomodulatory drugs for MS treatment have been developed that blunt the early inflammatory phase, reducing relapses and delaying progression. However, strategies for remyelination by generating new OLGs, in particular at the chronic or secondary progressive stage, when chronic lesions in the CNS have been established, remain a major challenge in this field.…”

Regulation of Oligodendrocyte Differentiation: Relevance for Remyelination

“…Although inflammation can promote remyelination and the immune response might therefore be beneficial for neuroregeneration in MS, MS is predominantly an inflammatory disease (Lassmann & van Horssen, 2011). Maintaining an acute inflammatory milieu in order to improve remyelination may therefore be harmful to the patient.…”

“…Moreover, reactive microglia can produce proinflammatory cytokines and reactive oxygen species. Therefore activated microglia may actually enhance the demyelination process (Lassmann & van Horssen, 2011).…”

Nano- and micro-based systems for immunotolerance induction in multiple sclerosis

“…1,2 In developed countries it is the second cause of neurological disability in young adults, with high burden for the patient, the family and the resources of the health system. 3 It is a complex disease and its underlying mechanisms are only partially understood.…”