Abstract Details

Title RNA-Binding Protein Altered Expression and Mislocalization in Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) S49 - Multiple Sclerosis: Basic Science (1:36 PM-1:48 PM)

Poster/Presentation
Number 004

Objective To determine whether there are RNA-binding protein (RBP) abnormalities in multiple sclerosis (MS).

Background Nuclear depletion and mislocalization into the cytoplasm of RNA-binding protein (RBP) trans-activation response DNA-binding protein of 43 kDa (TDP-43) is thought to contribute to the pathogenesis of amyotrophic lateral sclerosis. We recently found that TDP-43 as well as polypyrimidine tract binding protein (PTB) have decreased expression and mislocalization in oligodendrocytes (OLs) in demyelinated lesions in an experimental mouse model of MS caused by Theiler’s murine encephalomyelitis virus infection. Importantly, Wang et al. (2018) found that knockdown of TDP-43 in OLs of a mouse led to demyelination and cell death. Furthermore, PTB is critically important to splicing. The present study investigated whether there were RBP abnormalities in MS.

Design/Methods We investigated the localization and expression of TDP-43, FUS, and PTB in OLs and neurons in demyelinated lesions of MS.

Results We found: i) mislocalized TDP-43 in OLs in active demyelinating lesions in some MS patients; ii) decreased PTB1 expression in OLs in mixed active/inactive demyelinating lesions; iii) decreased nuclear expression of PTB2 in neurons in cortical demyelinating lesions.

Conclusions TDP-43 has been found to have a key role in OL function and viability, while PTB is important in neuronal differentiation, suggesting that altered expression and mislocalization of these RBPs in MS lesions may contribute to the pathogenesis of demyelination and neurodegeneration. Our findings also identify nucleocytoplasmic transport as a potential target for treatment.

Authors/Disclosures
Katsuhisa Masaki, MD (Kyushu university) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Alexandre Prat, MD (CHUM Hopital Norte Dame/ Dept of Neurology)	The institution of Dr. Prat has received research support from CIHR and MSSC.
Raymond P. Roos, MD, FAAN (University of Chicago Med Ctr)	Dr. Roos has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink. Dr. Roos has stock in Amazon. Dr. Roos has stock in Amgen. Dr. Roos has stock in Apple. Dr. Roos has stock in Cigna. Dr. Roos has stock in IBM. Dr. Roos has stock in Ionis. Dr. Roos has stock in Pfizer. Dr. Roos has received research support from Lohengrin Foundation.

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