ArticleJournal of neurochemistry2013
Over-expression of heat shock factor 1 phenocopies the effect of chronic inhibition of TOR by rapamycin and is sufficient to ameliorate Alzheimer's-like deficits in mice modeling the disease.
Article in Journal of neurochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.
- Exploitation of Autophagy Inducers in the Management of Dementia: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Rapamycin Reduces Amyloid-β Plaques and Improves Behavioral Performance in a Sex-Dependent Manner in Mouse Models of Amyloidosis.CNS neuroscience & therapeutics · 2026Article
- Adaptive inter-tissue proteostasis networks in aging and neurodegeneration.Bioscience reports · 2026Review
- mTOR signaling and Alzheimer's disease: What we know and where we are?CNS neuroscience & therapeutics · 2024Review
- Heat shock factor 1 drives regulatory T-cell induction to limit murine intestinal inflammation.Mucosal immunology · 2024Article
- HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023Review
- Rapamycin Responds to Alzheimer's Disease: A Potential Translational Therapy.Clinical interventions in aging · 2023Review
- Impaired autophagy in amyloid-beta pathology: A traditional review of recent Alzheimer's research.Journal of biomedical research · 2022Article
- AKT1 mediates multiple phosphorylation events that functionally promote HSF1 activation.The FEBS journal · 2022Article
- Multidimensional insights into the repeated electromagnetic field stimulation and biosystems interaction in aging and age-related diseases.Journal of biomedical science · 2022Review
- Genetic and pharmacologic proteasome augmentation ameliorates Alzheimer's-like pathology in mouse and fly APP overexpression models.Science advances · 2022Article
- Auxin-Inducible Degron System Reveals Temporal-Spatial Roles of HSF-1 and Its Transcriptional Program in Lifespan Assurance.Frontiers in aging · 2022Article
- Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration.Molecular neurodegeneration · 2021Review
- mTOR Attenuation with Rapamycin Reverses Neurovascular Uncoupling and Memory Deficits in Mice Modeling Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Repeated electromagnetic field stimulation lowers amyloid-β peptide levels in primary human mixed brain tissue cultures.Scientific reports · 2021Article
- Basic Limonoid modulates Chaperone-mediated Proteostasis and dissolve Tau fibrils.Scientific reports · 2020Article
- Modulation of Amyloid States by Molecular Chaperones.Cold Spring Harbor perspectives in biology · 2019Review
- Physical Activity Alleviates Cognitive Dysfunction of Alzheimer's Disease through Regulating the mTOR Signaling Pathway.International journal of molecular sciences · 2019Review
- Neuroprotective Effects of HSF1 in Retinal Ischemia-Reperfusion Injury.Investigative ophthalmology & visual science · 2019Article
- Rapamycin and Alzheimer's disease: Time for a clinical trial?Science translational medicine · 2019Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Rapamycin, an inhibitor of target-of-rapamycin, extends lifespan in mice, possibly by delaying aging. We recently showed that rapamycin halts the progression of Alzheimer's (AD)-like deficits, reduces amyloid-beta (Aβ) and induces autophagy in the human amyloid precursor protein (PDAPP) mouse model. To delineate the mechanisms by which chronic rapamycin delays AD we determined proteomic signatures in brains of control- and rapamycin-treated PDAPP mice. Proteins with reported chaperone-like activity were overrepresented among proteins up-regulated in rapamycin-fed PDAPP mice and the master regulator of the heat-shock response, heat-shock factor 1, was activated. This was accompanied by the up-regulation of classical chaperones/heat shock proteins (HSPs) in brains of rapamycin-fed PDAPP mice. The abundance of most HSP mRNAs except for alpha B-crystallin, however, was unchanged, and the cap-dependent translation inhibitor 4E-BP was active, suggesting that increased expression of HSPs and proteins with chaperone activity may result from preferential translation of pre-existing mRNAs as a consequence of inhibition of cap-dependent translation. The effects of rapamycin on the reduction of Aβ, up-regulation of chaperones, and amelioration of AD-like cognitive deficits were recapitulated by transgenic over-expression of heat-shock factor 1 in PDAPP mice. These results suggest that, in addition to inducing autophagy, rapamycin preserves proteostasis by increasing chaperones. We propose that the failure of proteostasis associated with aging may be a key event enabling AD, and that chronic inhibition of target-of-rapamycin may delay AD by maintaining proteostasis in brain. Read the Editorial Highlight for this article on doi: 10.1111/jnc.12098.
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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.