Electrophilic and Drug-Induced Stimulation of NOTCH3 N-terminal Fragment Oligomerization in Cerebrovascular Pathology.

ABSTRACT: Small vessel disease is a prevalent age-related condition linked to increased risk of dementia and stroke. We investigate the most commonly inherited form, CADASIL, caused by cysteine-involving mutations in NOTCH3. Recent studies highlight accumulation of NOTCH3 N-terminal fragmentation product (NTF) in disease. In vitro, NTF is capable of both spontaneous and catecholamine-enhanced cysteine-mediated oligomerization. Despite well-characterized genetic influence on CADASIL, environmental effects, including medication usage, on disease remain unclear. We studied effects of assorted electrophilic compounds and drugs on NTF oligomerization by SDS-PAGE and dynamic light scattering. We then examined direct proton pump inhibitor-NTF binding with antibodies designed against proton pump inhibitor-l

SUBMITTER: Young KZ 

PROVIDER: S-EPMC8557116 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature