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Updated: Apr 5, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Aggregation of MBP in chronic demyelination
Kati Frid1, Ofira Einstein1, Yael Friedman-Levi1
1Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital Jerusalem, 91120, Israel.
Objectives:
Misfolding of key disease proteins to an insoluble state is associated with most neurodegenerative conditions, such as prion, Parkinson, and Alzheimer's diseases. In this work, and by studying animal models of multiple sclerosis, we asked whether this is also the case for myelin basic protein (MBP) in the late and neurodegenerative phases of demyelinating diseases.
Methods:
To this effect, we tested whether MBP, an essential myelin component, present prion-like properties in animal models of MS, as is the case for Cuprizone-induced chronic demyelination or chronic phases of Experimental Autoimmune Encephalomyelitis (EAE).
Results:
We show here that while total levels of MBP were not reduced following extensive demyelination, part of these molecules accumulated thereafter as aggregates inside oligodendrocytes or around neuronal cells. In chronic EAE, MBP precipitated concomitantly with Tau, a marker of diverse neurodegenerative conditions, including MS. Most important, analysis of fractions from Triton X-100 floatation gradients suggest that the lipid composition of brain membranes in chronic EAE differs significantly from that of naïve mice, an effect which may relate to oxidative insults and subsequently prevent the appropriate insertion and compaction of new MBP in the myelin sheath, thereby causing its misfolding and aggregation.
Interpretation:
Prion-like aggregation of MBP following chronic demyelination may result from an aberrant lipid composition accompanying this pathological status. Such aggregation of MBP may contribute to neuronal damage that occurs in the progressive phase of MS.
Insights
Myelin basic protein (MBP) aggregates in neurodegenerative phases of multiple sclerosis (MS). This prion-like misfolding, linked to altered brain lipids, may drive neuronal damage in progressive MS.
Area of Science:
- Neuroscience
- Neuroimmunology
- Protein Misfolding Diseases
Background:
- Neurodegenerative diseases involve protein misfolding into insoluble aggregates.
- Multiple Sclerosis (MS) is a demyelinating disease affecting the central nervous system.
Purpose of the Study:
- Investigate if myelin basic protein (MBP) exhibits prion-like aggregation in animal models of MS.
- Determine MBP's role in the neurodegenerative phases of demyelinating diseases.
Main Methods:
- Studied animal models of multiple sclerosis (MS), including Cuprizone-induced demyelination and Experimental Autoimmune Encephalomyelitis (EAE).
- Assessed MBP aggregation and its co-precipitation with Tau.
- Analyzed brain membrane lipid composition using Triton X-100 floatation gradients.
Main Results:
- MBP did not decrease in total levels but formed aggregates within oligodendrocytes and around neurons in demyelinated areas.
- MBP co-precipitated with Tau in chronic EAE, a marker for neurodegeneration.
- Significant alterations in brain membrane lipid composition were observed in chronic EAE, potentially due to oxidative stress.
Conclusions:
- Prion-like aggregation of MBP in chronic demyelination may stem from aberrant lipid composition.
- MBP aggregation could contribute to neuronal damage in the progressive stages of MS.
