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Restoring hippocampal glucose metabolism rescues cognition across Alzheimer's disease pathologies.
Minhas, Paras S; Jones, Jeffrey R; Latif-Hernandez, Amira; Sugiura, Yuki; Durairaj, Aarooran S; Wang, Qian; Mhatre, Siddhita D; Uenaka, Takeshi; Crapser, Joshua; Conley, Travis; Ennerfelt, Hannah; Jung, Yoo Jin; Liu, Ling; Prasad, Praveena; Jenkins, Brenita C; Ay, Yeonglong Albert; Matrongolo, Matthew; Goodman, Ryan; Newmeyer, Traci; Heard, Kelly; Kang, Austin; Wilson, Edward N; Yang, Tao; Ullian, Erik M; Serrano, Geidy E; Beach, Thomas G; Wernig, Marius; Rabinowitz, Joshua D; Suematsu, Makoto; Longo, Frank M; McReynolds, Melanie R; Gage, Fred H; Andreasson, Katrin I.
Afiliação
  • Minhas PS; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Jones JR; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA 94305, USA.
  • Latif-Hernandez A; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Sugiura Y; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Durairaj AS; Central Institute for Experimental Medicine and Life Science, Keio University, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821, Japan.
  • Wang Q; WPI-Bio2Q Research Center, Keio University, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki 210-0821 Japan.
  • Mhatre SD; Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.
  • Uenaka T; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Crapser J; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Conley T; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Ennerfelt H; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Jung YJ; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Liu L; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Prasad P; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Jenkins BC; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Ay YA; Lewis Institute for Cancer Research, Princeton University, Princeton, NJ 08544, USA.
  • Matrongolo M; Department of Chemistry, Princeton University, Princeton 08544 NJ, USA.
  • Goodman R; Department of Biochemistry and Molecular Biology, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.
  • Newmeyer T; Department of Biochemistry and Molecular Biology, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA 16802, USA.
  • Heard K; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Kang A; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Wilson EN; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Yang T; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Ullian EM; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Serrano GE; Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Beach TG; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Wernig M; Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • Rabinowitz JD; Department of Ophthalmology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Suematsu M; Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ 85351, USA.
  • Longo FM; Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ 85351, USA.
  • McReynolds MR; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Gage FH; Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
  • Andreasson KI; Lewis Institute for Cancer Research, Princeton University, Princeton, NJ 08544, USA.
Science ; 385(6711): eabm6131, 2024 Aug 23.
Article em En | MEDLINE | ID: mdl-39172838
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 ß 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Astrócitos / Peptídeos beta-Amiloides / Indolamina-Pirrol 2,3,-Dioxigenase / Doença de Alzheimer / Glucose / Glicólise / Hipocampo / Cinurenina / Neurônios Limite: Animals / Humans / Male Idioma: En Revista: Science Ano de publicação: 2024 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Astrócitos / Peptídeos beta-Amiloides / Indolamina-Pirrol 2,3,-Dioxigenase / Doença de Alzheimer / Glucose / Glicólise / Hipocampo / Cinurenina / Neurônios Limite: Animals / Humans / Male Idioma: En Revista: Science Ano de publicação: 2024 Tipo de documento: Article