ELIZA

return kwic search for role out of >500 occurrences
507580 occurrences (No.24 in the rank) during 5 years in the PubMed. [cache]

427) 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).

--- ABSTRACT ---

PMID:33615187 DOI:10.1021/acsptsci.0c00217

2021 ACS pharmacology & translational science

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

- 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 protect both neurons and murine BECs from ischemia-reperfusion injury. Cultures of primary BECs from ALDH2 ^-/- mice that manifest enhanced oxidative stress were sensitive to ischemia, leading to reduced cell viability and loss of tight junction proteins; this damage was rescued by calpain-1 and cathepsin-B inhibitors. In ALDH2 ^-/- mice 24 h after mild traumatic brain injury (mTBI), BBB damage was reflected by significantly increased fluorescein extravasation and perturbation of tight junction proteins, eNOS, MMP-9, and GFAP. Both calpain and cathepsin-B inhibitors alleviated BBB dysfunction caused by mTBI. No clear advantage was shown by selective versus nonselective calpain inhibitors in these studies. The lack of recognition of the ability of calpain inhibitors to protect the BBB may have led to the premature abandonment of this therapeutic approach in AD clinical trials and requires further mechanistic studies of cerebrovascular protection by calpain-1 inhibitors.

--- ABSTRACT END ---

[
right
kwic]

[frequency of next (right) word to role]

(1)215 of	(4)9 null	(7)5 as
(2)199 in	(5)8 and	(8)3 by
(3)23 for	(6)6 that	(9)2 is

add keyword

--- WordNet output for role --- =>役目, 役割, 任務, 職務, 役 Overview of noun role The noun role has 4 senses (first 4 from tagged texts) 1. (34) function, office, part, role -- (the actions and activities assigned to or required or expected of a person or group; "the function of a teacher"; "the government must do its part"; "play its role") 2. (10) character, role, theatrical role, part, persona -- (an actor's portrayal of someone in a play; "she played the part of Desdemona") 3. (8) function, purpose, role, use -- (what something is used for; "the function of an auger is to bore holes"; "ballet is beautiful but what use is it?") 4. (6) role -- (normal or customary activity of a person in a particular social setting; "what is your role on the team?") --- WordNet end ---