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The impact of genetic variability on Alzheimer's therapies: obstacles for pharmacogenetic progress.
Expert Opin Drug Metab Toxicol
January 2025
EuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, Bergondo, Corunna, Spain.
Introduction: Genetic load influences the therapeutic response to conventional drugs in Alzheimer's disease (AD). Pharmacogenetics (PGx) is the best option to reduce drug-drug interactions and adverse drug reactions in patients undergoing polypharmacy regimens. However, there are important limitations that make it difficult to incorporate pharmacogenetics into routine clinical practice.
View Article and Find Full Text PDFThe interplay of sex and genotype in disease associations: a comprehensive network analysis in the UK Biobank.
Hum Genomics
January 2025
Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Richards Building B304, 3700 Hamilton Walk, Philadelphia, PA, 19104, USA.
Background: Disease comorbidities and longer-term complications, arising from biologically related associations across phenotypes, can lead to increased risk of severe health outcomes. Given that many diseases exhibit sex-specific differences in their genetics, our objective was to determine whether genotype-by-sex (GxS) interactions similarly influence cross-phenotype associations. Through comparison of sex-stratified disease-disease networks (DDNs)-where nodes represent diseases and edges represent their relationships-we investigate sex differences in patterns of polygenicity and pleiotropy between diseases.
View Article and Find Full Text PDFA comparative study on the antioxidant and antiglycation properties of different vitamin D forms.
Eur J Med Chem
January 2025
Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, 2c Mickiewicza Street, 15-233, Bialystok, Poland. Electronic address:
Vitamin D plays multiple roles in the body. Recently, there has been an increase in its popularity and growing interest in vitamin D supplementation. However, the mechanisms of vitamin D action have not yet been sufficiently explored.
View Article and Find Full Text PDFHEBE: A novel chimeric chronokine for ameliorating memory deficits in Alzheimer's disease.
Biomed Pharmacother
January 2025
Institut de Neurociències (INc), Universitat Autònoma Barcelona, Bellaterra 08193, Spain; Vall d'Hebron Institut de Recerca (VHIR), Barcelona 08035, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain. Electronic address:
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by amyloid-β and Tau protein depositions, with treatments focusing on single proteins have shown limited success due to the complexity of pathways involved. This study explored the potential of chronokines -proteins that modulate aging-related processes- as an alternative therapeutic approach. Specifically, we focused on a novel pleiotropic chimeric protein named HEBE, combining s-KL, sTREM2 and TIMP2, guided by bioinformatic analyses to ensure the preservation of each protein's conformation, crucial for their functions.
View Article and Find Full Text PDFProteasome inhibition induces microtubule-dependent changes in nuclear morphology.
iScience
January 2025
Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.
Cancers and neurodegenerative disorders are associated with both disrupted proteostasis and altered nuclear morphology. Determining if changes in nuclear morphology contribute to pathology requires an understanding of the underlying mechanisms, which are difficult to elucidate in cells where pleiotropic effects of altering proteostasis might indirectly influence nuclear morphology. To investigate direct effects, we studied nuclei assembled in egg extract where potentially confounding effects of transcription, translation, cell cycle progression, and actin dynamics are absent.
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