Régulation de la douleur au niveau de la biosynthèse protéinique

 

Arkady Khoutorsky

Université McGill

 

Domaine : neurosciences, santé mentale et toxicomanies

Programme Chercheurs-boursiers - Junior 1

Concours 2018-2019

Chronic pain is the leading cause of long-term disability and suffering in humans. Patients with chronic pain often exhibit depression, anxiety, and sleep disturbances. Numerous diseases and conditions can cause chronic pain. In most cases chronic pain is a result of lowering the threshold for a pain signal to be transmitted, a phenomenon called sensitization. Long-lasting sensitization of the pain pathway involves the synthesis of proteins to support changes in pain threshold; however, the mechanisms controlling the synthesis of the proteins as well as the identity and function of newly synthesised proteins have not been identified. The information encoded in our genes is first used as a template to generate a molecule called mRNA by a process called transcription. Then, new proteins are synthesized from the mRNAs in a process called mRNA translation. Both processes are tightly regulated and can affect the protein composition of the cell.

Most studies hitherto have focused on transcriptional regulation; however, recent work has shown that the abundance of proteins in the cell is determined to a large extent by the rate of mRNA translation. Inhibition of mRNA translation alleviates chronic pain in animal models; however, the molecular and cellular mechanisms underlying the beneficial effect of translation inhibitors remain elusive. This proposal aims to decipher mechanisms by which mRNA translation promotes pain sensitization by identifying mRNAs mediating these phenomena and studying their function. The study is expected to identify novel molecular targets and lead to the development of better therapeutics to relieve pain and improve quality of life of individuals living with pain.