The ketamine metabolite (2R,6R)-hydroxynorketamine rescues hippocampal mRNA translation, synaptic plasticity and memory in mouse models of Alzheimer's disease.
Alzheimer's & dementia : the journal of the Alzheimer's Association August 1, 2024 Felipe C Ribeiro, Danielle Cozachenco, Elentina K Argyrousi et al.
The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) activates signaling pathways (ERK1/2, mTOR, S6K1) in the hippocampus, rescuing long-term potentiation and memory deficits in two mouse models of Alzheimer's disease: mice infused with amyloid-β oligomers and aged APP/PS1 mice. The rescue depends on ERK signaling. HNK also corrects aberrant transcription in APP/PS1 mice. These results suggest HNK could be a therapeutic approach for Alzheimer's disease.