Document Detail


Multiple sclerosis as a neurodegenerative disease: pathology, mechanisms and therapeutic implications.
MedLine Citation:
PMID:  21455066     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: Multiple sclerosis (MS) treatments targeting the inflammatory nature of the disease have become increasingly effective in recent years. However, our efforts at targeting the progressive disease phase have so far been largely unsuccessful. This has led to the hypothesis that disease mechanisms independent of an adaptive immune response contribute to disease progression and closely resemble neurodegeneration.
RECENT FINDINGS: Nonfocal, diffuse changes in the MS brain, especially axonal loss and mitochondrial dysfunction, prove better correlates of disability than total lesion load and have been associated with disease progression. Molecular changes in nondemyelinated MS tissue also suggest that alterations in the MS brain are widespread and consist of pro-inflammatory as well as anti-inflammatory responses. However, local lymphocytic inflammation and microglial activation are salient features of the chronic disease, and T-cell-mediated inflammation contributes to tissue damage. In addition, neuroaxonal cytoskeletal alterations have been associated with disease progression.
SUMMARY: Our knowledge of the molecular mechanisms leading to neuroaxonal damage and demise in MS is steadily increasing. Experimental therapies targeting neuroaxonal ionic imbalances and energy metabolism in part show promising results. A better understanding of the molecular mechanisms underlying chronic progression will substantially aid the development of new treatment strategies.
Authors:
Christine Stadelmann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current opinion in neurology     Volume:  24     ISSN:  1473-6551     ISO Abbreviation:  Curr. Opin. Neurol.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-02     Completed Date:  2011-08-15     Revised Date:  2013-01-18    
Medline Journal Info:
Nlm Unique ID:  9319162     Medline TA:  Curr Opin Neurol     Country:  England    
Other Details:
Languages:  eng     Pagination:  224-9     Citation Subset:  IM    
Affiliation:
Institute of Neuropathology, University Medical Centre, Gottingen, Germany. cstadelmann@med.uni-goettingen.de
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MeSH Terms
Descriptor/Qualifier:
Axons / pathology,  physiology
Disease Progression
Humans
Immune System / physiopathology
Mitochondria / physiology
Multiple Sclerosis / pathology*,  physiopathology*,  therapy
Neurodegenerative Diseases / pathology*,  physiopathology*,  therapy
Neurons / pathology,  physiology

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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