Virus-like Intercellular Signaling Underlying Autoimmune Neurological Disorders

2023 Scientific Innovations Award
Jason Shepherd, Ph.D.
University of Utah

Dr. Shepherd’s lab discovered that a brain gene critical for memory and cognition, Arc, has biochemical properties like retroviruses such as HIV. Arc protein can form virus-like protein capsids that shuttle RNA and proteins cell-to-cell. Other human genes have predicted similarities, but it remains unknown if these genes have also retained virus-like properties. They found that another family of genes that are also expressed in the brain can form capsids. These paraneoplastic Ma antigen (PNMA) genes sometimes cause neurological disorders when abnormally expressed in certain kinds of cancers due to an autoimmune response. It is unclear how or why these proteins activate the immune system to generate self-antibodies. The aim of this project is to test whether abnormal expression of PNMA virus-like capsids outside the brain are the cause of auto-antibody production and the resulting neurological symptoms. This project will uncover new signaling pathways in the brain and reveal the causes of some autoimmune neurological disorders.

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