Aggregation of MBP in chronic demyelination.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital Jerusalem, 91120, Israel.
Kati
K
Frid
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital Jerusalem, 91120, Israel.
Ofira
O
Einstein
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital Jerusalem, 91120, Israel.
Yael
Y
Friedman-Levi
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital Jerusalem, 91120, Israel.
Orli
O
Binyamin
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital Jerusalem, 91120, Israel.
Tamir
T
Ben-Hur
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital Jerusalem, 91120, Israel.
Ruth
R
Gabizon