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Σάββατο 13 Οκτωβρίου 2018

Polymerase-1 pathway activation in acute multiple sclerosis relapse

Publication date: Available online 11 October 2018

Source: Autoimmunity Reviews

Author(s): Anat Achiron, Rina Falb, Anna Feldman, Maria Bovim, Onn Rosenblum, Ida Sarova Pinhas, David Magalashvili, Mark Dolev, Shay Menascu, Michael Gurevich

Abstract
Background

The operating molecular mechanisms that characterize a multiple sclerosis (MS) relapse has not been thoroughly studied. We have shown that increased expression of RNA polymerase 1 (POL1) molecular pathway is associated with increased MS disease activity.

Objective

To assess POL1 pathway expression during acute MS relapse.

Methods

We studied POL1 pathway activation and associated biomarkers during the first acute optic neuritis attack of MS, and in relapsing-remitting MS patients treated with disease-modifying drugs (DMDs) experiencing an acute MS relapse or a radiological relapse using gene expression microarrays and quantitative RT-PCR.

Results

In MS patients (N = 6) during the first acute optic neuritis attack POL1 pathway activation was evident by over-expression of POL1 related network including transcription factor UBTF and downstream components of Assembly of RNA POL1 complex (1.92E-03). POL1 related biomarkers RRN3, POLR1D and LRPPRC were over-expressed x1.6 (p = .002), ×1.7 (p = .01) and x2.0 (p = .001) times higher respectively, in MS patients (N = 30) during acute clinical relapse as compared with remission. Similarly, in MS patients (N = 21) that presented with a radiological relapse, we observed significant activation of POL1 related biomarkers including RRN3 (p = .01), POLR1D (p = .002), POLR1E (p = .0001) and LRPPRC (p = .006), as compared with remission, as well as overexpression of a large group of genes encoding ribosomal proteins like RPS6KA3 (p = 7.2E-6), RRP8 (p = .0002) and RPCS9 (p = .0008).

Conclusions

Our findings suggest that targeted inactivation of Pol-1 pathway may represent a novel strategy for a better treatment of acute MS relapse.



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