Related Experiment Video

Updated: Jun 27, 2026

An Ex vivo Model of an Oligodendrocyte-directed T-Cell Attack in Acute Brain Slices
06:36

An Ex vivo Model of an Oligodendrocyte-directed T-Cell Attack in Acute Brain Slices

Published on: February 5, 2015

Expression of TWEAK and its receptor Fn14 in the multiple sclerosis brain: implications for inflammatory tissue

Barbara Serafini1, Roberta Magliozzi, Barbara Rosicarelli

  • 1Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.

Journal of Neuropathology and Experimental Neurology
|November 20, 2008
PubMed

Insights

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor (Fn14) are upregulated in multiple sclerosis (MS) brain tissue. This TWEAK/Fn14 pathway indicates a potential therapeutic target for MS inflammation and injury.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system.
  • The role of specific inflammatory cytokines and their receptors in MS pathogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the expression patterns of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible 14 (Fn14), in postmortem brain tissue from MS patients and controls.
  • To determine the cellular sources and localization of TWEAK and Fn14 in relation to MS lesions and neuropathology.

Main Methods:

  • Immunohistochemistry was employed to visualize TWEAK and Fn14 expression in brain tissue.
  • Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify gene expression levels.
  • Analysis was performed on postmortem brain samples from individuals with MS and healthy controls.

Main Results:

  • Both TWEAK and Fn14 expression were significantly upregulated in MS brain tissue compared to controls.
  • TWEAK was primarily expressed by macrophages, astrocytes, and microglia associated with MS lesions, particularly at the edges of active white matter lesions and in cortical lesions.
  • Fn14 was predominantly found on neurons and reactive astrocytes in the cerebral cortex of MS brains.

Conclusions:

  • The TWEAK/Fn14 pathway is implicated in the inflammatory processes and tissue damage observed in multiple sclerosis.
  • Upregulation of TWEAK and Fn14 suggests this pathway is a potential therapeutic target for managing MS.
  • TWEAK may synergize with other factors to drive cortical injury in MS, especially in cases with meningeal inflammation.

More Related Videos

Two-photon Imaging of Cellular Dynamics in the Mouse Spinal Cord10:44

Two-photon Imaging of Cellular Dynamics in the Mouse Spinal Cord

Published on: February 22, 2015

Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines09:46

Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines

Published on: September 21, 2021

Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Multiple Sclerosis l: Introduction01:19

Multiple Sclerosis l: Introduction

Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) that affects the brain, spinal cord, and optic nerves. It is an inflammatory demyelinating disorder and a leading cause of neurological disability in young adults.EpidemiologyMS commonly begins between 20 and 40 years of age and is twice as common in women. Its exact cause remains unclear, but genetic susceptibility contributes, with higher risk in first-degree relatives and identical twins. A greater...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Tissue Injury: Inflammation and Repair01:28

Tissue Injury: Inflammation and Repair

Following injury, the integrity of the injured tissues must be reestablished. For example, in skin tissue, wound repair involves coordination among resident skin cells, blood mononuclear cells, extracellular matrix, growth factors, and cytokines to complete the healing cascade.
Formation of Blood Clot
In case of deep injuries, trauma to blood vessels results in blood loss. In the meantime, phospholipids released from the ruptured endothelial cellular membrane are converted into arachidonic...