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Reducing Timp3 or vitronectin ameliorates disease manifestations in CADASIL mice

Capone, Carmen ; Cognat, Emmanuel ; Ghezali, Lamia ; Baron-Menguy, Céline ; Aubin, Déborah ; Mesnard, Laurent ; Stöhr, Heidi ; Domenga-Denier, Valérie ; Nelson, Mark T. ; Joutel, Anne



Abstract

Objective: CADASIL is a genetic paradigm of cerebral small vessel disease caused by NOTCH3 mutations that stereo-typically lead to the extracellular deposition of NOTCH3 ectodomain (Notch(3ECD)) on the vessels. TIMP3 and vitronectin are 2 extracellular matrix proteins that abnormally accumulate in Notch3(ECD)-containing deposits on brain vessels of mice and patients with CADASIL. Herein, we ...

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