Understanding Molecular Mechanisms of NF1 Function and Regulation in the Nervous System
Abstract
Neurofibromatosis type 1 (NF1) is a devastating disorder that affects approximately one out of 3,000 people. In addition to developing tumors, NF1 patients suffer from prominent neuropsychiatric symptoms that include cognitive impairments, motor coordination problems, attention difficulties, and pain. The disease is caused by mutations in the gene that encodes neurofibromin protein, NF1. The focus of this proposal is on molecular mechanisms by which NF1 protein is regulated by cellular signaling systems and its role in controlling key neuronal pathways underlying neuropsychiatric manifestations. We hope that better understanding of the signaling mechanisms that lead to the nervous system dysfunction in NF1 will lead to an accelerated development of therapeutics mitigating the neuropsychiatric symptoms. This proposal is based on novel discovery of links between the NF1 and opioid system. The main goal of the proposal is to understand the role of NF1 in controlling responses mediated by the opioid G protein Coupled Receptors (GPCRs). Given extensive implication of GPCRs in pain and cognitive functions, it is likely that understanding the mechanisms of NF1 involvement in the process will provide a new point for therapeutic intervention. The relevance is particularly highlighted by the fact that GPCRs constitute prominent targets for pharmacological intervention, with many approved drugs in clinical practice used for a variety of neuropsychiatric ailments. It is anticipated that understanding NF1-GPCR interplay will substantially accelerate application of GPCR drugs for the treatment of neurofibromatosis.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910570
Entities
People
- Kirill A. Martemyanov
Organizations
- Scripps Research
- United States Army