Researchers Map Full-length Protein Involved in Chronic Pain, with Hopes for Future Therapies

Researchers Map Full-length Protein Involved in Chronic Pain, with Hopes for Future Therapies

Case Western Reserve University School of Medicine researchers have discovered the full-length structure of a protein named Transient Receptor Potential Vanilloid subtype 2 (TRPV2), with implications for the development of new treatments for chronic pain and cancer.

The paper, “Structure of the full-length TRPV2 channel by cryo-EM,” was published in Nature Communications. Researchers led by Dr. Vera Moiseenkova-Bell had previously established the link between TRPV2’s molecular mechanism in a study published in December 2015 in Molecular and Cellular Biology, titled “Nerve Growth Factor Regulates Transient Receptor Potential Vanilloid 2 via Extracellular Signal-Regulated Kinase Signaling to Enhance Neurite Outgrowth in Developing Neurons.

Moiseenkova-Bell’s team’s lab is the first to accurately and fully model TRPV2’s structure. The group used neuronal cells to reveal the previously unidentified molecular mechanism of the protein’s function in the process of neurite growth.

“By combining our findings regarding both this protein’s structure and molecular mechanism, we can investigate it with a more holistic understanding,” said Moiseenkova-Bell, Ph.D., principal investigator and assistant professor at Case Western’s School of Medicine Pharmacology Department, in a press release. “This positions us to develop pharmaceutical compounds that target TRPV2 as treatment for chronic pain.”

Moiseenkova-Bell’s team found that the outgrowth of sensory neurons under a neurotrophin-regulated signaling cascade might be caused partly due to TRPV2. Neurotrophin release in response to spinal injury may result in inflammatory signaling and abnormal outgrowth in peripheral sensory neurons, potentially leading to crippling chronic pain, a debilitating condition unlike acute pain – a state of alert to possible injury – that can last for months or even longer. It might be linked to a series of different medical conditions and it is frequently difficult to diagnose.

Researchers are hopeful that new therapeutic approaches for chronic pain and even treatments for malignant cancer cells can be found if they can fully understand the molecular mechanism and structures of proteins that cause abnormal growth, such as TRPV2.

“TRPV2 is expressed everywhere in the body, and has been shown to be involved in malignancy in neuroblastomas, prostate cancer, and bladder cancer. If we can study this protein in cancer cell lines, we could discover how it behaves and, in the long term, we may have more options to choose from when designing pharmaceutical compounds to treat these conditions,” Moiseenkova-Bell said.