Related Experiment Video
Updated: Feb 15, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding
Debbie A E Hendrickx1, Jackelien van Scheppingen1, Marlijn van der Poel1
1Neuroimmunology Research Group, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands.
Abstract:
In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1, and ANO4. Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16, and OLR1, and lipid uptake, such as CHIT1, GPNMB, and CCL18. Except CCL18, these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion.
Insights
Researchers identified key genes driving multiple sclerosis (MS) lesion activity and expansion. Targeting early demyelination mechanisms, particularly scavenger receptors, may halt lesion progression in MS patients.
Area of Science:
- Neuroimmunology
- Molecular Pathology
- Genomics
Background:
- Multiple sclerosis (MS) involves myelin phagocytosis by microglia and macrophages in active lesions.
- These lesions expand and eventually form sclerotic scars, indicating distinct pathological stages.
- Understanding the molecular drivers of lesion activity and cessation is crucial for MS treatment.
Purpose of the Study:
- To identify molecular mechanisms underlying the activity and halt of MS lesions.
- To analyze genome-wide gene expression in active and inactive MS lesions and surrounding tissues.
- To uncover novel genes and pathways involved in MS lesion development.
Main Methods:
- Genome-wide gene expression analysis of chronic active MS lesions, inactive MS lesions, and control tissues.
- Gene clustering to identify expression patterns associated with MS and lesion progression.
- In vitro experiments to assess the role of scavenger receptors in myelin uptake.
Main Results:
- Distinct gene expression patterns were identified for MS lesions and their developmental stages.
- Novel genes, including NPY, KANK4, NCAN, TKTL1, and ANO4, were regulated in active MS lesion rims.
- Upregulation of lipid binding and uptake genes (MSR1, CD68, CXCL16, OLR1, CHIT1, GPNMB, CCL18) in active lesions indicates foamy macrophage activity.
- These lipid-related genes, except CCL18, were also upregulated in regions surrounding active lesions, suggesting expansion.
- Downregulation of scavenger receptors MSR1 and CXCL16 reduced myelin uptake in vitro.
Conclusions:
- This study provides a comprehensive gene expression profile of MS pathology.
- Early demyelination, mediated by scavenger receptors, occurs in regions surrounding active MS lesions.
- Genes involved in early demyelination present promising therapeutic targets to halt MS lesion expansion.
Related Concept Videos
02:35Chromatin Position Affects Gene Expression
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
02:24Regulation of Expression Occurs at Multiple Steps
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
02:24Regulation of Expression Occurs at Multiple Steps
01:42What is Gene Expression?
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
01:36What is Gene Expression?
01:58Cell Specific Gene Expression