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[The evidence for primary axonal loss in multiple sclerosis].
D C Anthony1, P Hughes, V H Perry
1Grupo para las inflamaciones del SNC, Escuela de Ciencias Biológicas, University of Southampton, Inglaterra. d.anthony@soton.ac.uk
Revista De Neurologia
|August 10, 2000
Summary
Axon damage occurs in acute multiple sclerosis (MS) lesions, not just chronic ones. Matrix metalloproteinases (MMPs) are implicated in this axonal loss, suggesting new therapeutic targets for MS.
Area of Science:
- Neuroimmunology
- Pathogenesis of Multiple Sclerosis
- Axonal Injury Mechanisms
Context:
- Multiple Sclerosis (MS) is primarily viewed as a demyelinating disease.
- The timing and mechanisms of axonal damage in MS pathogenesis remain incompletely understood.
- Amyloid precursor protein (APP) immunoreactivity offers a sensitive method for detecting axonal damage.
Purpose:
- To investigate the occurrence of axon damage in acute MS lesions using APP immunoreactivity.
- To explore the role of matrix metalloproteinases (MMPs) in mediating axonal damage in MS.
Summary:
- APP staining revealed significant axonal damage in acute MS lesions and active lesion borders, with minimal expression in chronic lesions.
- Macrophages expressing MMPs are present in active MS lesions.
- Experimental evidence indicates MMPs can induce demyelination, blood-brain barrier breakdown, and axonal loss, and their inhibition mitigates MS-like lesions.
Impact:
- Findings suggest MS involves primary axonal loss alongside demyelination.
- MMPs represent a potential therapeutic target for reducing axonal damage in MS.
- This research reframes the understanding of MS as a disease with significant primary axonal pathology.