Extending the Calpain-Cathepsin Hypothesis to the Neurovasculature: Protection of Brain Endothelial Cells and Mice from Neurotrauma.

ABSTRACT: The calpain-cathepsin hypothesis posits a key role for elevated calpain-1 and cathepsin-B activity in the neurodegeneration underlying neurotrauma and multiple disorders including Alzheimer's disease (AD). AD clinical trials were recently halted on alicapistat, a selective calpain-1 inhibitor, because of insufficient exposure of neurons to the drug. In contrast to neuroprotection, the ability of calpain-1 and cathepsin-B inhibitors to protect the blood-brain barrier (BBB), is understudied. Since cerebrovascular dysfunction underlies vascular dementia, is caused by ischemic stroke, and is emerging as an early feature in the progression of AD, we studied protection of brain endothelial cells (BECs) by selective and nonselective calpain-1 and cathepsin-B inhibitors. We show these inhibitors p

SUBMITTER: Knopp RC 

PROVIDER: S-EPMC7887848 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature