Response of iPSC-derived neurons from individuals with treatment-resistant depression to (2 R,6 R)-hydroxynorketamine and reelin: an exploratory study.

ABSTRACT: Treatment-resistant depression (TRD) is associated with worse clinical outcomes and longer course of illness. However, TRD is more difficult to model in animal phenotypes, suggesting that other experimental and translational models must be considered to properly address and research novel therapeutics. Reelin, an endogenous glycoprotein downregulated in depression, has shown rapid antidepressant-like effects akin to those of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine. Interestingly, the antidepressant-like effects of both ketamine and reelin affect mechanistic target of rapamycin complex 1 (mTORC1) activity and that of its related downstream signalers. (2 R,6 R)-hydroxynorketamine (HNK) is a major metabolite of ketamine that, at therapeutic levels, appears to activate mT

SUBMITTER: Johnston JN 

PROVIDER: S-EPMC12705751 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature