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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
09:41

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis

Published on: July 19, 2019

A further TWEAK to multiple sclerosis pathophysiology

Arash Nazeri1, Pouria Heydarpour, Shokufeh Sadaghiani

  • 1Interdisciplinary Neuroscience Research Program, Tehran University of Medical Sciences, Tehran, Iran.

Molecular Neurobiology
|July 23, 2013
PubMed

Insights

The TWEAK-Fn14 pathway is implicated in multiple sclerosis (MS) pathogenesis. Blocking this axis shows promise in MS models by modulating neuroinflammation and neurodegeneration.

Area of Science:

  • Immunology
  • Neuroscience
  • Cell Biology

Background:

  • Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a TNF superfamily member regulating cellular functions.
  • TWEAK binds fibroblast growth factor-inducible 14 (Fn14), a receptor involved in cellular responses.
  • The TWEAK-Fn14 axis is increasingly recognized for its role in chronic autoimmune diseases.

Purpose of the Study:

  • To review the evidence for the TWEAK-Fn14 axis in multiple sclerosis (MS) pathophysiology.
  • To explore the role of this pathway in neuroinflammation, tissue remodeling, blood-brain barrier disruption, neurodegeneration, and astrogliosis.
  • To highlight the therapeutic potential of TWEAK-Fn14 axis blockade in MS models.

Main Methods:

  • Review of existing literature on TWEAK-Fn14 signaling in MS and experimental autoimmune encephalomyelitis (EAE).
  • Analysis of TWEAK and Fn14 expression in healthy and diseased brain tissue.
  • Examination of signaling pathways activated by TWEAK-Fn14, including NF-κB and MAPK.

Main Results:

  • TWEAK is expressed in microglia and macrophages within MS lesions, while absent in healthy brains.
  • TWEAK-Fn14 axis activation influences neuroinflammation, blood-brain barrier integrity, and neurodegeneration in MS.
  • Blockade of the TWEAK-Fn14 axis demonstrates therapeutic potential in EAE models.

Conclusions:

  • The TWEAK-Fn14 axis plays a significant role in the pathophysiology of multiple sclerosis.
  • Targeting the TWEAK-Fn14 pathway represents a promising therapeutic strategy for MS.
  • Further research into TWEAK-Fn14 signaling is crucial for understanding and treating MS.

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