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These findings emphasize that targeted antagonism of NMDA receptor signalling lowers body weight independently of MC4R, indicating that this preclinical drug candidate might not only be effective in treating polygenic obesity but also holds potential as an effective weight loss strategy for patients with loss-of-function mutations in MC4R , the most common form of monogenic obesity 32

found that endothelial cell dysfunction, which is characterized by low nitric oxide (NO) bioavailability, greater reactive oxygen species production, the activation of abscission enzymes, and impaired extracellular lysosome-associated organelle function, triggers the degradation of the EG (57), leading to shear stress defects