RapamycinFungusV1, Main, Exploration, bibRecord, 000725

TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease.

Identifieur interne : 000725 ( Main/Exploration ); précédent : 000724; suivant : 000726

TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease.

Auteurs : Tyler K. Ulland [États-Unis] ; Wilbur M. Song [États-Unis] ; Stanley Ching-Cheng Huang [États-Unis] ; Jason D. Ulrich [États-Unis] ; Alexey Sergushichev [Russie] ; Wandy L. Beatty [États-Unis] ; Alexander A. Loboda [Russie] ; Yingyue Zhou [États-Unis] ; Nigel J. Cairns [États-Unis] ; Amal Kambal [États-Unis] ; Ekaterina Loginicheva [États-Unis] ; Susan Gilfillan [États-Unis] ; Marina Cella [États-Unis] ; Herbert W. Virgin [États-Unis] ; Emil R. Unanue [États-Unis] ; Yaming Wang [États-Unis] ; Maxim N. Artyomov [États-Unis] ; David M. Holtzman [États-Unis] ; Marco Colonna [États-Unis]

Source :

Cell [ 1097-4172 ] ; 2017.

RBID : pubmed:28802038

Descripteurs français

KwdFr :
- AMP-Activated Protein Kinases (métabolisme), Animaux (MeSH), Autophagie (MeSH), Créatinine (analogues et dérivés), Créatinine (métabolisme), Glycoprotéines membranaires (génétique), Glycoprotéines membranaires (métabolisme), Humains (MeSH), Lectines de type C (métabolisme), Macrophages (métabolisme), Maladie d'Alzheimer (anatomopathologie), Maladie d'Alzheimer (métabolisme), Microglie (anatomopathologie), Microglie (métabolisme), Modèles animaux de maladie humaine (MeSH), Métabolisme énergétique (MeSH), Neurites (métabolisme), Plaque amyloïde (métabolisme), Récepteurs immunologiques (génétique), Récepteurs immunologiques (métabolisme), Souris (MeSH), Sérine-thréonine kinases TOR (métabolisme).
MESH :
- analogues et dérivés : Créatinine.
- anatomopathologie : Maladie d'Alzheimer, Microglie.
- génétique : Glycoprotéines membranaires, Récepteurs immunologiques.
- métabolisme : AMP-Activated Protein Kinases, Créatinine, Glycoprotéines membranaires, Lectines de type C, Macrophages, Maladie d'Alzheimer, Microglie, Neurites, Plaque amyloïde, Récepteurs immunologiques, Sérine-thréonine kinases TOR.
- Animaux, Autophagie, Humains, Modèles animaux de maladie humaine, Métabolisme énergétique, Souris.

English descriptors

KwdEn :
- AMP-Activated Protein Kinases (metabolism), Alzheimer Disease (metabolism), Alzheimer Disease (pathology), Animals (MeSH), Autophagy (MeSH), Creatinine (analogs & derivatives), Creatinine (metabolism), Disease Models, Animal (MeSH), Energy Metabolism (MeSH), Humans (MeSH), Lectins, C-Type (metabolism), Macrophages (metabolism), Membrane Glycoproteins (genetics), Membrane Glycoproteins (metabolism), Mice (MeSH), Microglia (metabolism), Microglia (pathology), Neurites (metabolism), Plaque, Amyloid (metabolism), Receptors, Immunologic (genetics), Receptors, Immunologic (metabolism), TOR Serine-Threonine Kinases (metabolism).
MESH :
- chemical , analogs & derivatives : Creatinine.
- chemical , genetics : Membrane Glycoproteins, Receptors, Immunologic.
- chemical , metabolism : AMP-Activated Protein Kinases, Creatinine, Lectins, C-Type, Membrane Glycoproteins, Receptors, Immunologic, TOR Serine-Threonine Kinases.
- metabolism : Alzheimer Disease, Macrophages, Microglia, Neurites, Plaque, Amyloid.
- pathology : Alzheimer Disease, Microglia.
- Animals, Autophagy, Disease Models, Animal, Energy Metabolism, Humans, Mice.

Abstract

Elevated risk of developing Alzheimer's disease (AD) is associated with hypomorphic variants of TREM2, a surface receptor required for microglial responses to neurodegeneration, including proliferation, survival, clustering, and phagocytosis. How TREM2 promotes such diverse responses is unknown. Here, we find that microglia in AD patients carrying TREM2 risk variants and TREM2-deficient mice with AD-like pathology have abundant autophagic vesicles, as do TREM2-deficient macrophages under growth-factor limitation or endoplasmic reticulum (ER) stress. Combined metabolomics and RNA sequencing (RNA-seq) linked this anomalous autophagy to defective mammalian target of rapamycin (mTOR) signaling, which affects ATP levels and biosynthetic pathways. Metabolic derailment and autophagy were offset in vitro through Dectin-1, a receptor that elicits TREM2-like intracellular signals, and cyclocreatine, a creatine analog that can supply ATP. Dietary cyclocreatine tempered autophagy, restored microglial clustering around plaques, and decreased plaque-adjacent neuronal dystrophy in TREM2-deficient mice with amyloid-β pathology. Thus, TREM2 enables microglial responses during AD by sustaining cellular energetic and biosynthetic metabolism.

DOI: 10.1016/j.cell.2017.07.023
PubMed: 28802038
PubMed Central: PMC5573224

Affiliations:

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Le document en format XML

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<author><name sortKey="Zhou, Yingyue" sort="Zhou, Yingyue" uniqKey="Zhou Y" first="Yingyue" last="Zhou">Yingyue Zhou</name>
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<author><name sortKey="Loginicheva, Ekaterina" sort="Loginicheva, Ekaterina" uniqKey="Loginicheva E" first="Ekaterina" last="Loginicheva">Ekaterina Loginicheva</name>
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<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Gilfillan, Susan" sort="Gilfillan, Susan" uniqKey="Gilfillan S" first="Susan" last="Gilfillan">Susan Gilfillan</name>
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<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Cella, Marina" sort="Cella, Marina" uniqKey="Cella M" first="Marina" last="Cella">Marina Cella</name>
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<country xml:lang="fr">États-Unis</country>
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<author><name sortKey="Virgin, Herbert W" sort="Virgin, Herbert W" uniqKey="Virgin H" first="Herbert W" last="Virgin">Herbert W. Virgin</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
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<author><name sortKey="Unanue, Emil R" sort="Unanue, Emil R" uniqKey="Unanue E" first="Emil R" last="Unanue">Emil R. Unanue</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
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<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
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<author><name sortKey="Wang, Yaming" sort="Wang, Yaming" uniqKey="Wang Y" first="Yaming" last="Wang">Yaming Wang</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
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<settlement type="city">Saint-Louis (Missouri)</settlement>
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<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
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<author><name sortKey="Artyomov, Maxim N" sort="Artyomov, Maxim N" uniqKey="Artyomov M" first="Maxim N" last="Artyomov">Maxim N. Artyomov</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
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<author><name sortKey="Holtzman, David M" sort="Holtzman, David M" uniqKey="Holtzman D" first="David M" last="Holtzman">David M. Holtzman</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
</author>
<author><name sortKey="Colonna, Marco" sort="Colonna, Marco" uniqKey="Colonna M" first="Marco" last="Colonna">Marco Colonna</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: mcolonna@wustl.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease.</title>
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<author><name sortKey="Song, Wilbur M" sort="Song, Wilbur M" uniqKey="Song W" first="Wilbur M" last="Song">Wilbur M. Song</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
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<author><name sortKey="Huang, Stanley Ching Cheng" sort="Huang, Stanley Ching Cheng" uniqKey="Huang S" first="Stanley Ching-Cheng" last="Huang">Stanley Ching-Cheng Huang</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
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<author><name sortKey="Ulrich, Jason D" sort="Ulrich, Jason D" uniqKey="Ulrich J" first="Jason D" last="Ulrich">Jason D. Ulrich</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
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<author><name sortKey="Sergushichev, Alexey" sort="Sergushichev, Alexey" uniqKey="Sergushichev A" first="Alexey" last="Sergushichev">Alexey Sergushichev</name>
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<country xml:lang="fr">Russie</country>
<wicri:regionArea>Computer Technologies Department, ITMO University, Saint Petersburg 197101</wicri:regionArea>
<wicri:noRegion>Saint Petersburg 197101</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Beatty, Wandy L" sort="Beatty, Wandy L" uniqKey="Beatty W" first="Wandy L" last="Beatty">Wandy L. Beatty</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
</author>
<author><name sortKey="Loboda, Alexander A" sort="Loboda, Alexander A" uniqKey="Loboda A" first="Alexander A" last="Loboda">Alexander A. Loboda</name>
<affiliation wicri:level="1"><nlm:affiliation>Computer Technologies Department, ITMO University, Saint Petersburg 197101, Russia.</nlm:affiliation>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Computer Technologies Department, ITMO University, Saint Petersburg 197101</wicri:regionArea>
<wicri:noRegion>Saint Petersburg 197101</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhou, Yingyue" sort="Zhou, Yingyue" uniqKey="Zhou Y" first="Yingyue" last="Zhou">Yingyue Zhou</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
</author>
<author><name sortKey="Cairns, Nigel J" sort="Cairns, Nigel J" uniqKey="Cairns N" first="Nigel J" last="Cairns">Nigel J. Cairns</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
</author>
<author><name sortKey="Kambal, Amal" sort="Kambal, Amal" uniqKey="Kambal A" first="Amal" last="Kambal">Amal Kambal</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
</author>
<author><name sortKey="Loginicheva, Ekaterina" sort="Loginicheva, Ekaterina" uniqKey="Loginicheva E" first="Ekaterina" last="Loginicheva">Ekaterina Loginicheva</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
</author>
<author><name sortKey="Gilfillan, Susan" sort="Gilfillan, Susan" uniqKey="Gilfillan S" first="Susan" last="Gilfillan">Susan Gilfillan</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
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<author><name sortKey="Cella, Marina" sort="Cella, Marina" uniqKey="Cella M" first="Marina" last="Cella">Marina Cella</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
</author>
<author><name sortKey="Virgin, Herbert W" sort="Virgin, Herbert W" uniqKey="Virgin H" first="Herbert W" last="Virgin">Herbert W. Virgin</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
</author>
<author><name sortKey="Unanue, Emil R" sort="Unanue, Emil R" uniqKey="Unanue E" first="Emil R" last="Unanue">Emil R. Unanue</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
</author>
<author><name sortKey="Wang, Yaming" sort="Wang, Yaming" uniqKey="Wang Y" first="Yaming" last="Wang">Yaming Wang</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
</author>
<author><name sortKey="Artyomov, Maxim N" sort="Artyomov, Maxim N" uniqKey="Artyomov M" first="Maxim N" last="Artyomov">Maxim N. Artyomov</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
</author>
<author><name sortKey="Holtzman, David M" sort="Holtzman, David M" uniqKey="Holtzman D" first="David M" last="Holtzman">David M. Holtzman</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
</author>
<author><name sortKey="Colonna, Marco" sort="Colonna, Marco" uniqKey="Colonna M" first="Marco" last="Colonna">Marco Colonna</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: mcolonna@wustl.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110</wicri:regionArea>
<placeName><region type="state">Missouri (État)</region>
<settlement type="city">Saint-Louis (Missouri)</settlement>
</placeName>
<orgName type="university">École de médecine (Université Washington de Saint-Louis)</orgName>
</affiliation>
</author>
</analytic>
<series><title level="j">Cell</title>
<idno type="eISSN">1097-4172</idno>
<imprint><date when="2017" type="published">2017</date>
</imprint>
</series>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>AMP-Activated Protein Kinases (metabolism)</term>
<term>Alzheimer Disease (metabolism)</term>
<term>Alzheimer Disease (pathology)</term>
<term>Animals (MeSH)</term>
<term>Autophagy (MeSH)</term>
<term>Creatinine (analogs & derivatives)</term>
<term>Creatinine (metabolism)</term>
<term>Disease Models, Animal (MeSH)</term>
<term>Energy Metabolism (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Lectins, C-Type (metabolism)</term>
<term>Macrophages (metabolism)</term>
<term>Membrane Glycoproteins (genetics)</term>
<term>Membrane Glycoproteins (metabolism)</term>
<term>Mice (MeSH)</term>
<term>Microglia (metabolism)</term>
<term>Microglia (pathology)</term>
<term>Neurites (metabolism)</term>
<term>Plaque, Amyloid (metabolism)</term>
<term>Receptors, Immunologic (genetics)</term>
<term>Receptors, Immunologic (metabolism)</term>
<term>TOR Serine-Threonine Kinases (metabolism)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>AMP-Activated Protein Kinases (métabolisme)</term>
<term>Animaux (MeSH)</term>
<term>Autophagie (MeSH)</term>
<term>Créatinine (analogues et dérivés)</term>
<term>Créatinine (métabolisme)</term>
<term>Glycoprotéines membranaires (génétique)</term>
<term>Glycoprotéines membranaires (métabolisme)</term>
<term>Humains (MeSH)</term>
<term>Lectines de type C (métabolisme)</term>
<term>Macrophages (métabolisme)</term>
<term>Maladie d'Alzheimer (anatomopathologie)</term>
<term>Maladie d'Alzheimer (métabolisme)</term>
<term>Microglie (anatomopathologie)</term>
<term>Microglie (métabolisme)</term>
<term>Modèles animaux de maladie humaine (MeSH)</term>
<term>Métabolisme énergétique (MeSH)</term>
<term>Neurites (métabolisme)</term>
<term>Plaque amyloïde (métabolisme)</term>
<term>Récepteurs immunologiques (génétique)</term>
<term>Récepteurs immunologiques (métabolisme)</term>
<term>Souris (MeSH)</term>
<term>Sérine-thréonine kinases TOR (métabolisme)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Creatinine</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Membrane Glycoproteins</term>
<term>Receptors, Immunologic</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>AMP-Activated Protein Kinases</term>
<term>Creatinine</term>
<term>Lectins, C-Type</term>
<term>Membrane Glycoproteins</term>
<term>Receptors, Immunologic</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" qualifier="analogues et dérivés" xml:lang="fr"><term>Créatinine</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Maladie d'Alzheimer</term>
<term>Microglie</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Glycoprotéines membranaires</term>
<term>Récepteurs immunologiques</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Alzheimer Disease</term>
<term>Macrophages</term>
<term>Microglia</term>
<term>Neurites</term>
<term>Plaque, Amyloid</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>AMP-Activated Protein Kinases</term>
<term>Créatinine</term>
<term>Glycoprotéines membranaires</term>
<term>Lectines de type C</term>
<term>Macrophages</term>
<term>Maladie d'Alzheimer</term>
<term>Microglie</term>
<term>Neurites</term>
<term>Plaque amyloïde</term>
<term>Récepteurs immunologiques</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Alzheimer Disease</term>
<term>Microglia</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Autophagy</term>
<term>Disease Models, Animal</term>
<term>Energy Metabolism</term>
<term>Humans</term>
<term>Mice</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Autophagie</term>
<term>Humains</term>
<term>Modèles animaux de maladie humaine</term>
<term>Métabolisme énergétique</term>
<term>Souris</term>
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<front><div type="abstract" xml:lang="en">Elevated risk of developing Alzheimer's disease (AD) is associated with hypomorphic variants of TREM2, a surface receptor required for microglial responses to neurodegeneration, including proliferation, survival, clustering, and phagocytosis. How TREM2 promotes such diverse responses is unknown. Here, we find that microglia in AD patients carrying TREM2 risk variants and TREM2-deficient mice with AD-like pathology have abundant autophagic vesicles, as do TREM2-deficient macrophages under growth-factor limitation or endoplasmic reticulum (ER) stress. Combined metabolomics and RNA sequencing (RNA-seq) linked this anomalous autophagy to defective mammalian target of rapamycin (mTOR) signaling, which affects ATP levels and biosynthetic pathways. Metabolic derailment and autophagy were offset in vitro through Dectin-1, a receptor that elicits TREM2-like intracellular signals, and cyclocreatine, a creatine analog that can supply ATP. Dietary cyclocreatine tempered autophagy, restored microglial clustering around plaques, and decreased plaque-adjacent neuronal dystrophy in TREM2-deficient mice with amyloid-β pathology. Thus, TREM2 enables microglial responses during AD by sustaining cellular energetic and biosynthetic metabolism.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28802038</PMID>
<DateCompleted><Year>2017</Year>
<Month>08</Month>
<Day>16</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>08</Month>
<Day>26</Day>
</DateRevised>
<Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1097-4172</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>170</Volume>
<Issue>4</Issue>
<PubDate><Year>2017</Year>
<Month>Aug</Month>
<Day>10</Day>
</PubDate>
</JournalIssue>
<Title>Cell</Title>
<ISOAbbreviation>Cell</ISOAbbreviation>
</Journal>
<ArticleTitle>TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease.</ArticleTitle>
<Pagination><MedlinePgn>649-663.e13</MedlinePgn>
</Pagination>
<ELocationID EIdType="pii" ValidYN="Y">S0092-8674(17)30830-9</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.cell.2017.07.023</ELocationID>
<Abstract><AbstractText>Elevated risk of developing Alzheimer's disease (AD) is associated with hypomorphic variants of TREM2, a surface receptor required for microglial responses to neurodegeneration, including proliferation, survival, clustering, and phagocytosis. How TREM2 promotes such diverse responses is unknown. Here, we find that microglia in AD patients carrying TREM2 risk variants and TREM2-deficient mice with AD-like pathology have abundant autophagic vesicles, as do TREM2-deficient macrophages under growth-factor limitation or endoplasmic reticulum (ER) stress. Combined metabolomics and RNA sequencing (RNA-seq) linked this anomalous autophagy to defective mammalian target of rapamycin (mTOR) signaling, which affects ATP levels and biosynthetic pathways. Metabolic derailment and autophagy were offset in vitro through Dectin-1, a receptor that elicits TREM2-like intracellular signals, and cyclocreatine, a creatine analog that can supply ATP. Dietary cyclocreatine tempered autophagy, restored microglial clustering around plaques, and decreased plaque-adjacent neuronal dystrophy in TREM2-deficient mice with amyloid-β pathology. Thus, TREM2 enables microglial responses during AD by sustaining cellular energetic and biosynthetic metabolism.</AbstractText>
<CopyrightInformation>Copyright © 2017 Elsevier Inc. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ulland</LastName>
<ForeName>Tyler K</ForeName>
<Initials>TK</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Song</LastName>
<ForeName>Wilbur M</ForeName>
<Initials>WM</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Huang</LastName>
<ForeName>Stanley Ching-Cheng</ForeName>
<Initials>SC</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ulrich</LastName>
<ForeName>Jason D</ForeName>
<Initials>JD</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sergushichev</LastName>
<ForeName>Alexey</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Computer Technologies Department, ITMO University, Saint Petersburg 197101, Russia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Beatty</LastName>
<ForeName>Wandy L</ForeName>
<Initials>WL</Initials>
<AffiliationInfo><Affiliation>Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Loboda</LastName>
<ForeName>Alexander A</ForeName>
<Initials>AA</Initials>
<AffiliationInfo><Affiliation>Computer Technologies Department, ITMO University, Saint Petersburg 197101, Russia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zhou</LastName>
<ForeName>Yingyue</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cairns</LastName>
<ForeName>Nigel J</ForeName>
<Initials>NJ</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kambal</LastName>
<ForeName>Amal</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Loginicheva</LastName>
<ForeName>Ekaterina</ForeName>
<Initials>E</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gilfillan</LastName>
<ForeName>Susan</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Cella</LastName>
<ForeName>Marina</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Virgin</LastName>
<ForeName>Herbert W</ForeName>
<Initials>HW</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Unanue</LastName>
<ForeName>Emil R</ForeName>
<Initials>ER</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>Yaming</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Artyomov</LastName>
<ForeName>Maxim N</ForeName>
<Initials>MN</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Holtzman</LastName>
<ForeName>David M</ForeName>
<Initials>DM</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Colonna</LastName>
<ForeName>Marco</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: mcolonna@wustl.edu.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
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<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 DK058177</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>T32 CA009547</GrantID>
<Acronym>CA</Acronym>
<Agency>NCI NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R21 AG059176</GrantID>
<Acronym>AG</Acronym>
<Agency>NIA NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>T32 AI007163</GrantID>
<Acronym>AI</Acronym>
<Agency>NIAID NIH HHS</Agency>
<Country>United States</Country>
</Grant>
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   |texte=   TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease.
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	Serveur d'exploration sur la rapamycine et les champignons
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TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease.

TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease.

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