Advancing age is the biggest risk factor for development for the major life-threatening diseases in industrialized nations accounting for >90% of deaths. Alzheimer's dementia (AD) is among the most devastating. Currently approved therapies fail to slow progression of the disease, providing only modest improvements in memory. Recently reported work describes mechanistic studies of J147, a promising therapeutic molecule previously shown to rescue the severe cognitive deficits exhibited by aged, transgenic AD mice. Apparently, J147 targets the mitochondrial alpha-F1-ATP synthase (ATP5A). Modest inhibition of the ATP synthase modulates intracellular calcium to activate AMP-activated protein kinase to inhibit mammalian target of rapamycin, a known mechanism of lifespan extension from worms to mammals.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1089/rej.2018.2056 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
High glucose affects the cardiac function of diabetic Akita mice by inhibiting cardiac ATP synthase beta subunit.
Int J Cardiol Cardiovasc Risk Prev
March 2025
Beijing Chaoyang Hospital, Capital Medical University, Department of Endocrinology, Beijing, China.
Object: To explore the mechanism of diabetic cardiomyopathy that hyperglycemia may affect the cardiac function by inhibiting the expression of ATPase β subunit.
Method: Cardiac function, fibrosis levels, and the expression of the ATPase β subunit were observed in Akita mice-a diabetes mice model without lipid metabolism disorders--using morphological, molecular biology, and echocardiographic analyses compared to wild-type mice. The study revealed a connection between the decreased ATPase β subunit and the development of diabetic myocardial injury.
The landscape of rare mitochondrial DNA variants in sudden cardiac death: A potential role for ATP synthase.
Heliyon
January 2025
Unit of Medical Genetics, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
Sudden cardiac death (SCD) is a major health concern, which can be the sign of a latent mitochondrial disease. However, mitochondrial DNA (mtDNA) contribution is largely unexplored in SCD at population level. Recently, mtDNA variants have been associated with congenital cardiopathy and higher risk of ischemic heart disease, suggesting them as potential risk factors also in SCD.
View Article and Find Full Text PDFDiscovery of 1,3,4-oxadiazin-5-one Derivative CJ1-34 as a Partial ATP Synthase Inhibitor for CNS Applications.
Chemistry
January 2025
ETH Zürich, Institute of Pharmaceutical Sciences, Höneggerberg, HCI H427, Vladimir Prelog Weg 4, 8093, Zürich, SWITZERLAND.
ATP synthase dysregulation has been implicated in many diseases, including cancer and neurodegenerative diseases. Whilst ATP synthase-targeting compounds have been reported, most are large or polar compounds and lack appropriate properties for a CNS drug. We designed, synthesised, and evaluated a novel series of ATP synthase targeting compounds, resulting in a 1,3,4-oxadiazin-5-one scaffold with improved physiochemical properties.
View Article and Find Full Text PDFEffect of High-Fat Diets on the Pharmacokinetics of Bedaquiline Fumarate Tablet: A Trial in Healthy Chinese Participants.
Clin Pharmacol Drug Dev
January 2025
Department of Clinical Research Center, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
Bedaquiline is employed to treat multidrug-resistant and extensive drug-resistant tuberculosis by inhibiting the proton pump of adenosine triphosphate synthase in Mycobacterium tuberculosis. This study aims to investigate the effect of high-fat diets on the pharmacokinetics of bedaquiline through a single-center, open-label, randomized trial in healthy Chinese participants. Bedaquiline fumarate tablets were administered at a dosage of 100 mg under both fasted conditions and high-fat diet conditions.
View Article and Find Full Text PDFLong Non-Coding RNA LOC113219358 Regulates Immune Responses in Through Protein Interactions.
Int J Mol Sci
January 2025
Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China.
Long non-coding RNAs (lncRNAs) are emerging as critical regulators in honeybee physiology, influencing development, behavior, and stress responses. This study investigates the role of lncRNA LOC113219358 in the immune response and neurophysiological regulation of brains. Using RNA interference (RNAi) and RNA sequencing (RNA-seq), we demonstrate that silencing lncLOC113219358 significantly alters the expression of 162 mRNA transcripts, including genes associated with detoxification, energy metabolism, and neuronal signaling.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!