Restoring hippocampal glucose metabolism rescues cognition across Alzheimer’s disease pathologies-Reference-Cited by-同舟云学术

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

Published:2024-08-23 Issue:6711 Volume:385 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Minhas Paras S.¹²^ORCID,Jones Jeffrey R.³^ORCID,Latif-Hernandez Amira¹,Sugiura Yuki⁴⁵⁶^ORCID,Durairaj Aarooran S.¹^ORCID,Wang Qian¹^ORCID,Mhatre Siddhita D.¹^ORCID,Uenaka Takeshi⁷^ORCID,Crapser Joshua¹^ORCID,Conley Travis¹^ORCID,Ennerfelt Hannah¹^ORCID,Jung Yoo Jin¹^ORCID,Liu Ling⁸⁹,Prasad Praveena¹⁰^ORCID,Jenkins Brenita C.¹⁰^ORCID,Ay Yeonglong Albert¹^ORCID,Matrongolo Matthew¹,Goodman Ryan³^ORCID,Newmeyer Traci³,Heard Kelly³^ORCID,Kang Austin³^ORCID,Wilson Edward N.¹^ORCID,Yang Tao¹^ORCID,Ullian Erik M.¹¹^ORCID,Serrano Geidy E.¹²^ORCID,Beach Thomas G.¹²^ORCID,Wernig Marius⁷¹³^ORCID,Rabinowitz Joshua D.⁸⁹^ORCID,Suematsu Makoto⁴⁵^ORCID,Longo Frank M.¹²^ORCID,McReynolds Melanie R.⁸⁹¹⁰^ORCID,Gage Fred H.³^ORCID,Andreasson Katrin I.¹²¹⁴¹⁵^ORCID

Affiliation:

1. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.

2. Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.

3. Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

4. Central Institute for Experimental Medicine and Life Science, Keio University, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.

5. WPI-Bio2Q Research Center, Keio University, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821 Japan.

6. Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.

7. Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.

8. Lewis Institute for Cancer Research, Princeton University, Princeton, NJ 08544, USA.

9. Department of Chemistry, Princeton University, Princeton 08544 NJ, USA.

10. Department of Biochemistry and Molecular Biology, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.

11. Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94143, USA.

12. Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ 85351, USA.

13. Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.

14. Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.

15. The Phil and Penny Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute, Stanford University, CA 94305, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

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

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