ArticleThe Journal of experimental medicine2017
Tau deletion promotes brain insulin resistance.
Article in The Journal of experimental medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 2 of them syntheses that pooled it.
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Who cites it
120 citing papers in PubMed, 2 syntheses or guidelines pooled it, 199 citations in OpenAlex.
- The Role of Protein Misfolding and Tau Oligomers (TauOs) in Alzheimer's Disease (AD).International journal of molecular sciences · 2019Pooled it
- Benzodiazepines and Related Drugs as a Risk Factor in Alzheimer's Disease Dementia.Frontiers in aging neuroscience · 2019Pooled it
- Insulin Regulates AKT/GSK-3β Signalling, Tau Phosphorylation, and Redox Homeostasis in SH-SY5Y Neuroblastoma Cells.International journal of molecular sciences · 2026Article
- Atypical involvement of Alzheimer's tau proteins in diseases beyond tauopathies.Life medicine · 2026Review
- Insulin Signaling in Alzheimer's Disease: Association with Brain Insulin Resistance.International journal of molecular sciences · 2026Review
- Tau protein: Physiological functions and multifaceted roles in neurodegenerative and psychiatric disorders.Genomic psychiatry : advancing science from genes to society · 2025Article
- A genome-wide association study identified 10 novel genomic loci associated with intrinsic capacity.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Regulation of tau protein by circCwc27: shared pathogenic mechanisms in type 2 diabetes mellitus and Alzheimer's disease.Brain informatics · 2025Article
- Harnessing Metabolism to Combat Neurodegeneration: Strategies for Reversing Age-Related Cognitive Decline.ACS pharmacology & translational science · 2025Review
- Cognitive Dysfunction and Dementia in Type 2 Diabetes Mellitus: Insights into Mechanisms, Models, and Therapeutics.ACS pharmacology & translational science · 2025Review
- Non-enzymatic posttranslational protein modifications in protein aggregation and neurodegenerative diseases.RSC chemical biology · 2025Review
- Microtubule-Associated Proteins (MAPs) Are Multifunctional Cytoskeletal Proteins in the Testis That Regulate Spermatogenesis.Advances in experimental medicine and biology · 2025Review
- Dysregulation of energy metabolism in Alzheimer's disease.Journal of neurology · 2024Review
- Article
- Untangling the role of tau in sex hormone responsive cancers: lessons learnt from Alzheimer's disease.Clinical science (London, England : 1979) · 2024Review
- Danggui Shaoyao San Alleviates Early Cognitive Impairment in Alzheimer's Disease Mice Through IRS1/GSK3β/Wnt3a-β-Catenin Pathway.Brain and behavior · 2024Article
- FTLD-MAPT mutations and short 5'UTR Tau mRNAs increase Tau translation.NAR molecular medicine · 2024Article
- Latest Perspectives on Alzheimer's Disease Treatment: The Role of Blood-Brain Barrier and Antioxidant-Based Drug Delivery Systems.Molecules (Basel, Switzerland) · 2024Review
- Resistance training boosts lactate transporters and synaptic proteins in insulin-resistance mice.Heliyon · 2024Article
- Truncated tau interferes with the autophagy and endolysosomal pathway and results in lipid accumulation.Cellular and molecular life sciences : CMLS · 2024Article
60 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular pathways underlying tau pathology-induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, and fibrillization of tau impair synaptic plasticity and cause degeneration. However, tau pathology may also result in the loss of specific physiological tau functions, which are largely unknown but could contribute to neuronal dysfunction. In the present study, we uncovered a novel function of tau in its ability to regulate brain insulin signaling. We found that tau deletion leads to an impaired hippocampal response to insulin, caused by altered IRS-1 and PTEN (phosphatase and tensin homologue on chromosome 10) activities. Our data also demonstrate that tau knockout mice exhibit an impaired hypothalamic anorexigenic effect of insulin that is associated with energy metabolism alterations. Consistently, we found that tau haplotypes are associated with glycemic traits in humans. The present data have far-reaching clinical implications and raise the hypothesis that pathophysiological tau loss-of-function favors brain insulin resistance, which is instrumental for cognitive and metabolic impairments in Alzheimer's disease patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.