Related Experiment Video
Updated: Apr 8, 2026
An Ex vivo Model of an Oligodendrocyte-directed T-Cell Attack in Acute Brain Slices
Published on: February 5, 2015
Microglia and necroptosis: The culprits of neuronal cell death in multiple sclerosis
Suhayl Dhib-Jalbut1, Dhan V Kalvakolanu2
1Department of Neurology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Abstract:
Multiple Sclerosis is an inflammatory demyelinating and degenerative disease of the central nervous system in which activated microglia contribute to oligodendroglial, neuronal, and axonal damage. A recent study (summarized here) provided evidence for a role of necroptosis in MS brain tissue based on reduced caspase-8 and increased expression of cFLIP in microglial cells. In addition, activation of RIPK1, RIPK3, and MLKL (molecules characteristic of necroptosis) was demonstrated in cortical lesions from MS brain specimens. Defective caspase-8 activity in microglia adds a new dimension to microglial role in MS and provides a potential therapeutic target in the progressive forms of the disease.
Insights
Necroptosis, a form of programmed cell death, plays a role in Multiple Sclerosis (MS) brain tissue. Targeting defective caspase-8 activity in microglia may offer a new therapeutic strategy for progressive MS.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Multiple Sclerosis (MS) involves central nervous system inflammation and neurodegeneration.
- Activated microglia contribute to neuronal and axonal damage in MS.
- The precise mechanisms of microglial-mediated damage in MS are still under investigation.
Purpose of the Study:
- To investigate the role of necroptosis in Multiple Sclerosis brain tissue.
- To explore the involvement of caspase-8 and its regulators in microglial cells in MS.
- To identify potential therapeutic targets for progressive MS.
Main Methods:
- Analysis of MS brain tissue for markers of necroptosis.
- Assessment of caspase-8 activity and cFLIP expression in microglial cells.
- Detection of RIPK1, RIPK3, and MLKL activation in cortical lesions.
Main Results:
- Evidence suggests a role for necroptosis in MS brain.
- Reduced caspase-8 and increased cFLIP expression were observed in microglial cells.
- Activation of key necroptosis molecules (RIPK1, RIPK3, MLKL) was confirmed in MS lesions.
Conclusions:
- Defective caspase-8 activity in microglia represents a novel aspect of microglial function in MS.
- These findings highlight necroptosis as a potential therapeutic target for progressive Multiple Sclerosis.
Related Concept Videos
01:16Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...