ArticleCell chemical biology2025
β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain.
Article in Cell chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The effect of exogenous ketone bodies on cognition across health and disease: a systematic review and meta-analysis.Frontiers in nutrition · 2026Pooled it
- A Randomized Open-Label, Observational Study of the Novel Ketone Ester, Bis Octanoyl (R)-1,3-Butanediol, and Its Acute Effect on ß-Hydroxybutyrate and Glucose Concentrations in Healthy Older Adults.Journal of nutrition in gerontology and geriatricsTrial
- RagC senses β-hydroxybutyrate abundancy to suppress mTORC1.Protein & cell · 2026Article
- Insights on geroscience pre-clinical and clinical trials to promote healthy aging from the Intrinsic Capacity, Frailty and Sarcopenia Research Task Force 2025.The Journal of frailty & aging · 2026Review
- Review
- Ketone body β-hydroxybutyrate restores neuronal Tau proteostasis via ketolysis-independent mechanism.bioRxiv : the preprint server for biology · 2026Article
- Mediterranean, MIND, and ketogenic diets in Alzheimer's disease: mechanistic coherence and clinical uncertainty.Frontiers in nutrition · 2026Article
- Ketogenic diet and Parkinson's disease.Frontiers in molecular neuroscience · 2026Review
- The Effect of Saffron Extract Supplementation During Resistance Training on Hippocampal Doublecortin and Hepatic β-Hydroxybutyrate Levels in Rats With Type 2 Diabetes.Journal of diabetes research · 2026Article
- Exercise-induced β-hydroxybutyrate contributes to cognitive improvement in aging mice.Journal of sport and health science · 2025Article
- NLRP3 Inflammasome in Stress-Related Neuropsychiatric Disorders: Mechanisms of Neuron-Microglia-Astrocyte Crosstalk, HPA Axis Dysregulation, and Therapeutic Perspective.Biomolecules · 2025Review
- The Effect of Exogenous Ketone Bodies on Cognition in Patients with Mild Cognitive Impairment, Alzheimer's Disease and in Healthy Adults: A Systematic Review and Meta-Analysis.medRxiv : the preprint server for health sciences · 2025Article
- 3-Hydroxybutyrate, a metabolite in sustaining neuronal cell vitality: a mendelian randomization and in vitro experimentation.Nutrition & metabolism · 2025Article
- Review
- Article
- Article
- A randomized open-label, observational study of the novel ketone ester, bis octanoyl (R)-1,3-butanediol, and its acute effect on ß-hydroxybutyrate and glucose concentrations in healthy older adults.medRxiv : the preprint server for health sciences · 2024Article
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24 authors.
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Abstract
Loss of proteostasis is a hallmark of aging and Alzheimer disease (AD). We identify β-hydroxybutyrate (βHB), a ketone body, as a regulator of protein solubility. βHB primarily provides ATP substrate during periods of reduced glucose availability, and regulates other cellular processes through protein interactions. We demonstrate βHB-induced protein insolubility is not dependent on covalent protein modification, pH, or solute load, and is observable in mouse brain in vivo after delivery of a ketone ester. This mechanism is selective for pathological proteins such as amyloid-β, and exogenous βHB ameliorates pathology in nematode models of amyloid-β aggregation toxicity. We generate libraries of the βHB-induced protein insolublome using mass spectrometry proteomics, and identify common protein domains and upstream regulators. We show enrichment of neurodegeneration-related proteins among βHB targets and the clearance of these targets from mouse brain. These data indicate a metabolically regulated mechanism of proteostasis relevant to aging and AD.
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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 Socratic graph.