Pro-Inflammatory Cytokines and Antibodies Induce hnRNP A1 Dysfunction in Mouse Primary Cortical Neurons

Muxue Li; Rachel Hamilton; Hannah E Salapa; Michael C Levin

doi:10.3390/brainsci11101282

Pro-Inflammatory Cytokines and Antibodies Induce hnRNP A1 Dysfunction in Mouse Primary Cortical Neurons

Brain Sci. 2021 Sep 28;11(10):1282. doi: 10.3390/brainsci11101282.

Authors

Muxue Li¹, Rachel Hamilton¹, Hannah E Salapa^{2

3}, Michael C Levin^{1

2

3}

Affiliations

¹ Department of Anatomy, Physiology, and Pharmacology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
² Office of the Saskatchewan Multiple Sclerosis Clinical Research Chair, University of Saskatchewan, Saskatoon, SK S7N 0M7, Canada.
³ Department of Medicine, Neurology Division, University of Saskatchewan, Saskatoon, SK S7N 0X8, Canada.

Abstract

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system with a significant neurodegenerative component. Dysfunctional RNA-binding proteins (RBPs) are causally linked to neuronal damage and are a feature of MS, including the mislocalization of the RBP heterogeneous nuclear ribonucleoprotein A1 (A1). Here, we show that primary neurons exposed to pro-inflammatory cytokines and anti-A1 antibodies, both characteristic of an MS autoimmune response, displayed increased A1 mislocalization, stress granule formation, and decreased neurite length, a marker of neurodegeneration. These findings illustrate a significant relationship between secreted immune factors, A1 dysfunction, and neuronal damage in a disease-relevant model system.

Keywords: RNA-binding protein; autoimmunity; cytokines; heterogeneous nuclear ribonucleoprotein A1; multiple sclerosis; stress granules.

Grants and funding

N/A/University of Saskatchewan