1. Pro-Inflammatory Cytokines and Antibodies Induce hnRNP A1 Dysfunction in Mouse Primary Cortical Neurons
- Author
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Muxue Li, Rachel Hamilton, Hannah E. Salapa, and Michael C. Levin
- Subjects
RNA-binding protein ,multiple sclerosis ,stress granules ,heterogeneous nuclear ribonucleoprotein A1 ,cytokines ,autoimmunity ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - 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.
- Published
- 2021
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