Cerebral infarction is a disease in which the stenosis or obstruction of cerebral blood vessels causes a deficiency of oxygen and energy in the brain, and damage to brain cells causes death of cranial nerve cells.Thalidomide is a drug that was discontinued in the past due to fetal malformations when taken by pregnant women, and has recently been reported to have a protective effect on nerve cell death in a cerebral ischemia model as an effect on neurological diseases. However, the detailed molecular mechanism was unknown.

　So far, the research group has identified cereblon (CRBN) as a binding protein to thalidomide.It was revealed that this protein has an inhibitory effect on cell death, and that AMP-activated protein kinase (AMPK), which is an energy sensor that maintains homeostasis in vivo, binds directly to CRBN.It is said that phosphorylation amplification occurs under cerebral ischemia, and it was thought that dephosphorylation of AMPK leads to neuroprotection.

　In this study, in order to investigate the efficacy of thalidomide for cerebral infarction and intracellular signals, we created and analyzed a rat middle cerebral artery occlusion / reperfusion model used as a model to mimic human cerebral infarction.As a result, thalidomide may regulate the activity of AMPK by changing the interaction between AMPK and cereblon via its target molecule, CRBN, and suppress neuronal cell death due to cerebral ischemia. Revealed.

　In the future, it is expected that the development of safer and more stable thalidomide derivatives and drugs that strengthen the binding between AMPK and CRBN will lead to the development of drugs that are effective for cerebral infarction.

Paper information:[Scientific Reports] The Neuroprotective Effect of Thalidomide against Ischemia through the Cereblon -mediated Repression of AMPK Activity