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Alzheimers Dement
December 2024
Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Washington University School of Medicine, St. Louis, MO, USA; Knight Alzheimer Disease Research Center, St. Louis, MO, USA.
Although amyloid b immunotherapies offer great potential for prevention or delay of symptoms in dominantly inherited AD (DIAD), the mechanism of action of this class of medications does not address the underlying mechanism of most DIAD mutations. Moreover, the need for repeated IV infusions or sub-cutaneous injections with Ab immunotherapies may prove challenging for long-term prevention approaches. The majority of DIAD mutations appear to affect the interaction of the gamma-secretase enzyme with the Amyloid Precursor Protein (APP) making this enzyme an attractive target for disease modification.
View Article and Find Full Text PDFThe Metabolic Treatabolome and Inborn Errors of Metabolism Knowledgebase therapy tool: Do not miss the opportunity to treat!
J Inherit Metab Dis
January 2025
Department of Pediatrics, Emma Children's Hospital, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.
Inborn errors of metabolism (IEMs) are rare genetic conditions with significant morbidity and mortality. Technological advances have increased therapeutic options, making it challenging to remain up to date. A centralized therapy knowledgebase is needed for early diagnosis and targeted treatment.
View Article and Find Full Text PDFDNA methylation modulates nucleosome retention in sperm and H3K4 methylation deposition in early mouse embryos.
Nat Commun
January 2025
Friedrich Miescher Institute for Biomedical Research, Fabrikstrasse 24, 4056, Basel, Switzerland.
In the germ line and during early embryogenesis, DNA methylation (DNAme) undergoes global erasure and re-establishment to support germ cell and embryonic development. While DNAme acquisition during male germ cell development is essential for setting genomic DNA methylation imprints, other intergenerational roles for paternal DNAme in defining embryonic chromatin are unknown. Through conditional gene deletion of the de novo DNA methyltransferases Dnmt3a and/or Dnmt3b, we observe that DNMT3A primarily safeguards against DNA hypomethylation in undifferentiated spermatogonia, while DNMT3B catalyzes de novo DNAme during spermatogonial differentiation.
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