Protein restriction slows the development and progression of pathology in a mouse model of Alzheimer's disease.

Animals Alzheimer Disease / pathology Disease Models, Animal Female Mice, Transgenic Male Mice Disease Progression Brain / metabolism Diet, Protein-Restricted Humans Mechanistic Target of Rapamycin Complex 1 / metabolism Autophagy Glucose Intolerance / metabolism Sphingolipids / metabolism Cognition Mice, Inbred C57BL

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
18 Jun 2024
Historique:
received: 25 09 2023
accepted: 12 06 2024
medline: 19 6 2024
pubmed: 19 6 2024
entrez: 18 6 2024
Statut: epublish

Résumé

Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer's disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also reduces AD pathology and mTORC1 activity, increases autophagy, and improves the cognition of 3xTg mice. Finally, PR improves the survival of 3xTg mice. Our results suggest that PR or pharmaceutical interventions that mimic the effects of this diet may hold promise as a treatment for AD.

Identifiants

DOI: 10.1038/s41467-024-49589-z PMID: 38890307
pubmed: 38890307
doi: 10.1038/s41467-024-49589-z
pii: 10.1038/s41467-024-49589-z
doi:

Substances chimiques

Mechanistic Target of Rapamycin Complex 1 EC 2.7.11.1
Sphingolipids 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

5217

Subventions

Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : AG056771, AG062328, AG061635, AG081482, AG084156
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : F31AG081115
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : AG082504
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)
ID : DK125859
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)
ID : R01DK133479
Organisme : Alzheimer's Association
ID : 23AARG-1029665
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)
ID : R35GM151130

Informations de copyright

© 2024. The Author(s).

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Auteurs

Reji Babygirija (R)

Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
Cellular and Molecular Biology Graduate Program, University of Wisconsin-Madison, Madison, WI, USA.

Michelle M Sonsalla (MM)

Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
Comparative Biomedical Sciences, University of Wisconsin-Madison, Madison, WI, USA.
ORCID: 0000-0001-8493-1416

Jericha Mill (J)

Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.

Isabella James (I)

Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Integrated Program in Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.

Jessica H Han (JH)

Cellular and Molecular Biology Graduate Program, University of Wisconsin-Madison, Madison, WI, USA.
Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.

Cara L Green (CL)

Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
ORCID: 0000-0002-2293-9364

Mariah F Calubag (MF)

Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
Cellular and Molecular Biology Graduate Program, University of Wisconsin-Madison, Madison, WI, USA.

Gina Wade (G)

Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Integrated Program in Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.

Anna Tobon (A)

Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.

John Michael (J)

Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.

Michaela M Trautman (MM)

Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
Nutrition and Metabolism Graduate Program, University of Wisconsin-Madison, Madison, WI, USA.

Ryan Matoska (R)

Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.

Chung-Yang Yeh (CY)

Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.

Isaac Grunow (I)

Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.

Heidi H Pak (HH)

Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
Nutrition and Metabolism Graduate Program, University of Wisconsin-Madison, Madison, WI, USA.
ORCID: 0000-0002-3287-6133

Michael J Rigby (MJ)

Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Neuroscience Training Program, University of Wisconsin-Madison, Madison, WI, 53705, USA.
ORCID: 0000-0001-8809-2648

Dominique A Baldwin (DA)

Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI, 53706, USA.

Natalie M Niemi (NM)

Department of Biochemistry & Molecular Biophysics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
ORCID: 0000-0002-5174-4005

John M Denu (JM)

Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Nutrition and Metabolism Graduate Program, University of Wisconsin-Madison, Madison, WI, USA.

Luigi Puglielli (L)

Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.
William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
ORCID: 0000-0003-0259-8424

Judith Simcox (J)

Cellular and Molecular Biology Graduate Program, University of Wisconsin-Madison, Madison, WI, USA.
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Integrated Program in Biochemistry, University of Wisconsin-Madison, Madison, WI, 53706, USA.
Nutrition and Metabolism Graduate Program, University of Wisconsin-Madison, Madison, WI, USA.
Howard Hughes Medical Institute, University of Wisconsin-Madison, Madison, WI, 53706, USA.
ORCID: 0000-0001-7350-6342

Dudley W Lamming (DW)

Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA. dlamming@medicine.wisc.edu.
William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. dlamming@medicine.wisc.edu.
Cellular and Molecular Biology Graduate Program, University of Wisconsin-Madison, Madison, WI, USA. dlamming@medicine.wisc.edu.
Comparative Biomedical Sciences, University of Wisconsin-Madison, Madison, WI, USA. dlamming@medicine.wisc.edu.
Nutrition and Metabolism Graduate Program, University of Wisconsin-Madison, Madison, WI, USA. dlamming@medicine.wisc.edu.
ORCID: 0000-0002-0079-4467

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Protein restriction slows the development and...
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Protein restriction slows the development and...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Protein restriction slows the development and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Protein restriction slows the development and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Protein restriction slows the development and...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Protein restriction slows the development and...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Protein restriction slows the development and...
questionsmedicales.fr › Phénomènes physiologiques › Alimentation et nutrition › Phénomènes physiologiques nutritionnels › Régime alimentaire › Régime pauvre en protéines › Protein restriction slows the development and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Protein restriction slows the development and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Sérine-thréonine kinases TOR › Complexe-1 cible mécanistique de la rapamycine › Protein restriction slows the development and...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Autophagie › Protein restriction slows the development and...
questionsmedicales.fr › Maladies métaboliques et nutritionnelles › Maladies métaboliques › Troubles du métabolisme du glucose › Hyperglycémie › Intolérance au glucose › Protein restriction slows the development and...
questionsmedicales.fr › Lipides › Lipides membranaires › Sphingolipides › Protein restriction slows the development and...
questionsmedicales.fr › Phénomènes psychologiques › Processus mentaux › Cognition › Protein restriction slows the development and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Protein restriction slows the development and...