Molecules, Vol. 24, Pages 4090: b-Annulated Halogen-Substituted Indoles as Potential DYRK1A Inhibitors
Molecules, Vol. 24, Pages 4090: [b]-Annulated Halogen-Substituted Indoles as Potential DYRK1A Inhibitors Molecules doi: 10.3390/molecules24224090 Authors: Christian Lechner Maren Flaßhoff Hannes Falke Lutz Preu Nadége Loaëc Laurent Meijer Stefan Knapp Apirat Chaikuad Conrad Kunick Since hyperactivity of the protein kinase DYRK1A is linked to several neurodegenerative disorders, DYRK1A inhibitors have been suggested as potential therapeutics for Down syndrome and Alzheimer’s disease. Most published inhibitors to date suffer from low selectivity against related kinases or from unfavorable physicochemical properties. In order to identify DYRK1A inhibitors with improved properties, a series of new chemicals based on [b]-annulated halogenated indoles were designed, synthesized, and evaluated for biological activity. Analysis of crystal structures revealed a typical type-I binding mode of the new inhibitor 4-chlorocyclohepta[b]indol-10(5H)-one in DYRK1A, exploiting mainly shape complementarity for tight binding. Conversion of the DYRK1A inhibitor 8-chloro-1,2,3,9-tetrahydro-4H-carbazol-4-one into a corresponding Mannich base hydrochloride improved the aqueous solubility but abrogated kinase inhibitory activity.
Authors: Silverstein NM, Pitheckoff N, Dugan E Abstract Engaging gerontology students in research that hits "close-to-home" can have lasting benefits for them and their communities both professionally and personally. Since 2016, cohorts of undergraduate/certificate students in an online applied research in aging course have explored healthy aging in their Massachusetts' (MA) communities. The students utilized both primary and secondary data sources. First, they extracted data from the 2014-2015 healthy aging data report (HADR) community profiles of 367 MA communities. Then they conducted in-person in...
AbstractPreclinical experiments and clinical trials demonstrated that angiotensin II AT1 receptor overactivity associates with aging and cellular senescence and that AT1 receptor blockers (ARBs) protect from age-related brain disorders. In a primary neuronal culture submitted to glutamate excitotoxicity, gene set enrichment analysis (GSEA) revealed expression of several hundred genes altered by glutamate and normalized by candesartan correlated with changes in expression in Alzheimer ’s patient’s hippocampus. To further establish whether our data correlated with gene expression alterations associated with aging...
Low-dose hydromethylthionine may help prevent both cognitive decline and brain atrophy in early Alzheimer's disease, new exploratory research suggests.Medscape Medical News
Conclusion: The evidence from the present study suggests that T allele of CD33 rs3865444 polymorphism is associated with LOAD in the studied Iranian population. PMID: 31799158 [PubMed]
Spain's Grifols said on Friday the latest results from a clinical trial of its Alzheimer's treatment show positive effects by achieving a reduction of the disease's progression in patients with mild and moderate conditions.
Incidence varied considerably by region, ranging from 0 to more than 3 percent across population areas in 2014
Publication date: December 2019Source: Canadian Journal of Cardiology, Volume 35, Issue 12Author(s): Sarah Cohen, Michelle Z. Gurvitz, Virginie Beauséjour-Ladouceur, Patrick R. Lawler, Judith Therrien, Ariane J. MarelliAbstractAs life expectancy in patients with congenital heart disease (CHD) has improved, the risk for developing noncardiac morbidities is increasing in adult patients with CHD (ACHD). Among these noncardiac complications, malignancies significantly contribute to the disease burden of ACHD patients. Epidemiologic studies of cancer risk in CHD patients are challenging because they require large numbers...
CONCLUSION: We demonstrated that EVOO therapy may prevent the risk of patients with MCI to progress to AD via decreasing fibrinolytic factors PAI-1 and a2 antiplasmin that reflecting in the diminution of the hallmarks proteins of AD, tau and Aβ amyloid as well and in a biomarker of oxidative stress, MDA. PMID: 31802059 [PubMed - in process]