Molecular mechanisms linking neuroinflammation and neurodegeneration in MS

Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disorder of the central nervous system (CNS) and one of the leading causes of neurological deficits and disability in young adults in western countries. Current medical treatment mainly influences disease progression via immunomodulatory or immunosuppressive actions. Indeed, MS research has been foremost focused on inflammation in the CNS, but more recent evidence suggests that chronic disability in MS is caused by neurodegeneration. Imaging studies show an early involvement of neurodegeneration as brain atrophy and gray matter lesions can be observed at disease onset. Thus, neuroprotective treatment strategies and the elucidation of the molecular mechanisms underlying neurodegeneration in MS have attracted the attention of the scientific community. Experimental autoimmune encephalomyelitis (EAE; the most commonly used animal model for MS), novel in-vivo imaging techniques such as two-photon microscopy and recently discovered molecular changes have offered new insights into the pathogenesis of neuroinflammation as well as neurodegeneration in MS. This review focuses on the interaction between components of the immune system and the neuronal compartment, as well as describing the most important molecular mechanisms that lead to axonal and neuronal degeneration in MS and EAE. (C) 2014 Published by Elsevier Inc.