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Further, evidence suggests that it also has a neuroprotective effect, reducing both oxidative stress and inflammatory response, but the exact molecular mechanisms of thalidomide on the brain were unknown.
To investigate, scientists at Waseda University and Tokyo University of Pharmacy and Life Sciences studied thalidomide's target protein, cereblon (CRBN), and its binding protein, AMP-activated protein kinase (AMPK), which plays an important role in maintaining intracellular energy homeostasis in the brain. Through their study, they revealed that thalidomide inhibits the activity of AMPK via CRBN under oxidative stress and suppresses nerve cell death.
Findings - Development - Thalidomide - Derivatives - Naoya
"We hope that our findings will help with the development of new and safer thalidomide derivatives," says Naoya Sawamura, associate professor of neuropharmacology at Waseda University and leading author of this study, "to better treat diseases such as cerebral infarction, a type of stroke which is a major cause of death worldwide."
Their study was published online in Scientific Reports on February 6, 2018.
Sawamura - Research - Group - Ischemia - Model
Specifically, Sawamura's research group used cerebral ischemia model rats of the cerebral artery occlusion/reperfusion (MCAO/R) to examine the effect of thalidomide on infarct lesions caused by cerebral ischemia and related intracellular signals. After performing qualitative analysis and assessments on the rats' physical movements, they found that thalidomide treatment significantly decreased the...
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