HtrA1L364P Leads to Cognitive Dysfunction and Vascular Destruction Through TGF-β/Smad Signaling Pathway in CARASIL Model Mice

The study on CARASIL model mice with the HtrA1L364P mutation demonstrated significant cognitive dysfunction and vascular damage through the TGF-β/Smad signaling pathway. Using 90 mice, researchers found that mutant mice had impaired learning and memory, disordered vascular structures, and increased TGF-β, Smad2, and Smad3 expression. Pathological analysis revealed endothelial cell hyperplasia and myelin sheath abnormalities. These findings suggest that the HtrA1L364P mutation disrupts TGF-β signaling, leading to ECM deposition and vascular pathology, which impairs brain function.