Restoring hippocampal glucose metabolism rescues cognition across Alzheimer’s disease pathologies Minhas 2024

Abstract
Impaired cerebral glucose metabolism is a pathologic feature of Alzheimer’s disease (AD), with recent proteomic studies highlighting disrupted glial metabolism in AD. We report that inhibition of indoleamine-2,3-dioxygenase 1 (IDO1), which metabolizes tryptophan to kynurenine (KYN), rescues hippocampal memory function in mouse preclinical models of AD by restoring astrocyte metabolism. Activation of astrocytic IDO1 by amyloid β and tau oligomers increases KYN and suppresses glycolysis in an aryl hydrocarbon receptor–dependent manner. In amyloid and tau models, IDO1 inhibition improves hippocampal glucose metabolism and rescues hippocampal long-term potentiation in a monocarboxylate transporter–dependent manner. In astrocytic and neuronal cocultures from AD subjects, IDO1 inhibition improved astrocytic production of lactate and uptake by neurons. Thus, IDO1 inhibitors presently developed for cancer might be repurposed for treatment of AD.

https://www.science.org/doi/10.1126/science.abm6131

 

https://scitechdaily.com/stanford-r...ine-in-alzheimers-with-brain-metabolism-drug/


Stanford Reverses Cognitive Decline in Alzheimer’s With Brain Metabolism Drug

 

Can anyone access the name of the IDO1 inhibitor they used? Thanks.

 

In mice... Must be the 100th time Alzheimers has been solved in mice...

 

It’s this—there is human data actually


A phase 1 study of PF-06840003, an oral indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor in patients with recurrent malignant glioma


https://pubmed.ncbi.nlm.nih.gov/32436060/