Anavex Life Sciences Corp (AVXL)

[georgejjl]

Anavex’s blarcamesine and/or Anavex 3-71 probably will prove to be very good treatments for CKD

PRE-084 ameliorated kidney injury by reducing endoplasmic reticulum stress in the rat model of adenine-induced chronic kidney disease
Mohanapriya Kumaran et al. Mol Biol Rep. 2023 Apr.

Background: Endoplasmic reticulum (ER) stress plays an important role in the development of chronic kidney disease (CKD). Sigma-1 receptors (s1Rs) are novel chaperone proteins that regulate ER stress. However, effect of s1R activation on renal ER stress is yet unexplored. So, in the present study we investigated the effects of PRE-084, a s1R agonist on renal injury and ER stress in the rat model of CKD.

Methods: CKD group rats were fed adenine for 28 days and CKD treatment group rats were additionally administered PRE-084 intraperitoneally at 1, 3 and 10 mg/kg body weight dose from Day 22-28. ER stress markers were evaluated using molecular biology techniques such as immunohistochemistry and Western blot.

Results: Marked kidney injury was observed in CKD rats as revealed by biochemical and histological findings. Expression of ER stress proteins such as phosphorylated protein kinase R-like ER kinase (p-PERK), cleaved activating transcription factor-6 (ATF-6f), phosphorylated inositol requiring enzyme1a (p-IRE1a) and caspase-12 were higher in CKD rats. Nevertheless, CKD rats treated with PRE-084 particularly at 10 mg/kg dose showed considerably lesser kidney injury along with higher expression of s1R and marked reduction of all the ER stress proteins studied.

Conclusion: Results reveal that PRE-084 likely ameliorated the adenine-induced kidney injury by lowering ER stress through increased s1R expression.

https://pubmed.ncbi.nlm.nih.gov/36826683/

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