ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2017
mTOR and neuronal cell cycle reentry: How impaired brain insulin signaling promotes Alzheimer's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Disentangling the inverse relationship between cancer and Alzheimer's or Parkinson's disease: A systematic review on Mendelian randomization studies.Neurobiology of disease · 2025Pooled it
- Prediction of differentially expressed microRNAs in blood as potential biomarkers for Alzheimer's disease by meta-analysis and adaptive boosting ensemble learning.Alzheimer's research & therapy · 2021Pooled it
- Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Post-Covid Alzheimer and Its Remediation via PROTACs Therapy: A Comprehensive Review.Health science reports · 2026Article
- 4R-tau isoform induction via TDP-43 in neurons in response to insulin: converging signaling pathways with implications for neurodegenerative disease.Acta neuropathologica communications · 2025Article
- From Fundamentals to Innovation in Alzheimer's Disease: Molecular Findings and Revolutionary Therapies.International journal of molecular sciences · 2024Review
- Disrupted mitochondrial response to nutrients is a presymptomatic event in the cortex of the APPAlzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- A common molecular and cellular pathway in developing Alzheimer and cancer.Biochemistry and biophysics reports · 2024Review
- Structural and functional damage to neuronal nuclei caused by extracellular tau oligomers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Dysregulation of mTOR by tau in Alzheimer's disease.Cytoskeleton (Hoboken, N.J.) · 2024Review
- Simufilam suppresses overactive mTOR and restores its sensitivity to insulin in Alzheimer's disease patient lymphocytes.Frontiers in aging · 2023Article
- Expression level comparison of marker genes related to early embryonic development and tumor growth.Oncology letters · 2022Article
- Aberrant crosstalk between insulin signaling and mTOR in young Down syndrome individuals revealed by neuronal-derived extracellular vesicles.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- SOD1 mediates lysosome-to-mitochondria communication and its dysregulation by amyloid-β oligomers.Neurobiology of disease · 2022Article
- A Mutant Variant of E2F4 Triggers Multifactorial Therapeutic Effects in 5xFAD Mice.Molecular neurobiology · 2022Article
- A human-based multi-gene signature enables quantitative drug repurposing for metabolic disease.eLife · 2022Article
- Transcriptome and Translatome Regulation of Pathogenesis in Alzheimer's Disease Model Mice.Journal of Alzheimer's disease : JAD · 2022Article
- PROTACs technology for treatment of Alzheimer's disease: Advances and perspectives.Acta materia medica · 2022Article
- Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration.Molecular neurodegeneration · 2021Review
- mTOR in Alzheimer disease and its earlier stages: Links to oxidative damage in the progression of this dementing disorder.Free radical biology & medicine · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
A major obstacle to presymptomatic diagnosis and disease-modifying therapy for Alzheimer's disease (AD) is inadequate understanding of molecular mechanisms of AD pathogenesis. For example, impaired brain insulin signaling is an AD hallmark, but whether and how it might contribute to the synaptic dysfunction and neuron death that underlie memory and cognitive impairment has been mysterious. Neuron death in AD is often caused by cell cycle reentry (CCR) mediated by amyloid-β oligomers (AβOs) and tau, the precursors of plaques and tangles. We now report that CCR results from AβO-induced activation of the protein kinase complex, mTORC1, at the plasma membrane and mTORC1-dependent tau phosphorylation, and that CCR can be prevented by insulin-stimulated activation of lysosomal mTORC1. AβOs were also shown previously to reduce neuronal insulin signaling. Our data therefore indicate that the decreased insulin signaling provoked by AβOs unleashes their toxic potential to cause neuronal CCR, and by extension, neuron death.
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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.