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beta-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain

2 weeks 5 days ago
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...
Sidharth S Madhavan

Extracellular vesicle-packed microRNAs profiling in Alzheimer's disease: The molecular intermediary between pathology and diagnosis

2 weeks 5 days ago
MicroRNAs (miRNAs), referring to a type of non-coding RNAs functioning in various biological processes, participate in the pathophysiology of Alzheimer's disease (AD) through increasing amyloid-beta (Aβ) production, enhancing Tau phosphorylation, and inducing neuroinflammation. Meanwhile, extracellular vesicles (EVs) have been suggested as promising carriers of AD biomarkers as they possess the ability to transmit information from cerebral tissue to peripheral blood. Inspired by the above...
Sandila Arif

β-hydroxybutyrate is a metabolic regulator of proteostasis in the aged and Alzheimer disease brain

2 weeks 5 days ago
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...
Sidharth S Madhavan

Age-related clonal hematopoiesis and HIV infection are associated with geriatric outcomes: The ARCHIVE study

2 weeks 5 days ago
While HIV infection and clonal hematopoiesis (CH) have been linked with inflammatory dysregulation and an increased risk of aging-related comorbidities, their relationship with clinical geriatric syndromes has not been well defined. In the Age-related Clonal Haematopoiesis in an HIV Evaluation Cohort (ARCHIVE) study (NCT04641013), we measure associations between HIV and CH and geriatric syndromes. Of 345 participants (176 with HIV and 169 without HIV), 23% had at least one mutation associated...
Win Min Han