====== VX-765 ======

Inflammatory [[Caspase-1]] has a significant impact on AD-like pathophysiology and [[Caspase-1 inhibitor]], [[VX-765]], reverses cognitive deficits in AD mouse models. Here, a one-month pre-symptomatic treatment of Swedish/Indiana mutant amyloid precursor protein (APPSw/Ind) J20 and wild-type mice with VX-765 delays both APPSw/Ind- and age-induced episodic and spatial memory deficits. VX-765 delays inflammation without considerably affecting soluble and aggregated amyloid beta peptide (Aβ) levels. Episodic memory scores correlate negatively with microglial activation. These results suggest that Caspase-1-mediated inflammation occurs early in the disease and raise hope that VX-765, a previously Food and Drug Administration-approved drug for human CNS clinical trials, may be a useful drug to prevent the onset of cognitive deficits and brain inflammation in AD
((Flores J, Noël A, Foveau B, Beauchet O, LeBlanc AC. Pre-symptomatic Caspase-1 inhibitor delays cognitive decline in a mouse model of Alzheimer disease and aging. Nat Commun. 2020 Sep 11;11(1):4571. doi: 10.1038/s41467-020-18405-9. Erratum in: Nat Commun. 2021 Apr 9;12(1):2271. PMID: 32917871; PMCID: PMC7486940.)).
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VX765 can counteract neurological damage after TBI by reducing pyroptosis and HMGB1/TLR4/NF-κB pathway activities. VX765 may have a good therapeutic effect on TBI
((Sun Z, Nyanzu M, Yang S, Zhu X, Wang K, Ru J, Yu E, Zhang H, Wang Z, Shen J, Zhuge Q, Huang L. VX765 Attenuates Pyroptosis and HMGB1/TLR4/NF-κB Pathways to Improve Functional Outcomes in TBI Mice. Oxid Med Cell Longev. 2020 Apr 15;2020:7879629. doi: 10.1155/2020/7879629. PMID: 32377306; PMCID: PMC7181015.))