1. Statins, cholesterol and cognition at the time of Alzheimer's disease diagnosis : cross-sectional study from the Swedish registry for cognitive/dementia disordersBojana Petek, Minjia Mo, Hong Xu, Jakob Norgren, Minh Tuan Hoang, Marta Villa-Lopez, Henrike Häbel, Julianna Kele, Luana Naia, Milica Gregorič Kramberger, 2025, original scientific article Abstract: Background: Evidence suggests statins may influence cognition in Alzheimer's disease (AD), but specific use patterns in AD patients remain unclear. Objective: To identify factors influencing statin use in AD and explore associations between statins, cholesterol, and cognition, evaluated with Mini-Mental State Examination (MMSE) at dementia diagnosis. Methods: A cross-sectional study using data from the Swedish Registry for Dementia and Cognitive Disorders (SveDem) and Stockholm Creatinine Measurements (SCREAM) from 2007 to 2018. Multivariable logistic regression examined associations between baseline characteristics and statin use, while linear regression analyzed relationships between statins, cholesterol levels, and MMSE scores. Results: We included 3074 AD patients (mean age 78.1 years; 59.4% women), of whom 1028 used statins (79.6% simvastatin, 20.4% atorvastatin). Patients with diabetes mellitus, ischemic heart disease, or stroke had greater odds of receiving statins. Older patients had slightly lower odds of receiving any statin at baseline (simvastatin use OR 0.98, 95% CI 0.97–0.99). Simvastatin users had 0.53 points higher MMSE on average at baseline compared to non-users of statins (se 0.23, p = 0.021). Higher low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels were associated with higher MMSE in non-users of statins, but not in statin users. Conclusions: Younger AD patients and those with cardiovascular disease were more likely to use statins. Simvastatin use was linked to higher cognitive scores at diagnosis. In non-users, higher LDL-C, TC, and HDL-C levels correlated with better baseline cognitive scores. Longitudinal studies are needed to investigate the effects of statins on cognitive decline in AD.
Keywords: Alzheimer's disease, cholesterol, dementia, drug repurposing, mini-mental state examination
Published in DiRROS: 15.04.2026; Views: 297; Downloads: 138
 Full text (915,97 KB) |
2. Thiol-reactive or redox-active : revising a repurposing screen led to a new invalidation pipeline and identified a true noncovalent inhibitor against papain-like protease from SARS-CoV-2Maria Kuzikov, Stefano Morasso, Jeanette Reinshagen, Markus Wolf, Vittoria Monaco, Flora Cozzolino, Simona Golič Grdadolnik, Primož Šket, Janez Plavec, Daniela Iaconis, 2025, original scientific article Abstract: The SARS-CoV-2 papain-like protease PLpro has multiple roles in the viral replication cycle, related to both its polypeptide cleavage function and its ability to antagonize the host immune response. Targeting the PLpro function is recognized as a promising mechanism to modulate viral replication, while supporting host immune responses. However, the development of PLpro-specific inhibitors remains challenging. Comprehensive investigations utilizing enzymatic, binding studies, and cellular assays revealed the previously reported inhibitors to act in an unspecific manner. At present, GRL-0617 and its derivatives remain the best-validated compounds with demonstrated antiviral activity in cells and in mouse models. In this study, we refer to the pitfalls of the redox sensitivity of PLpro. Using a screening-based approach to identify inhibitors of PLpro’s proteolytic activity, we made extensive efforts to validate active compounds over a range of conditions and readouts, emphasizing the need for comprehensive orthogonal data when profiling putative PLpro inhibitors. The remaining active compound, CPI-169, was shown to be a noncovalent inhibitor capable of competing with GRL-0617 in NMR-based experiments, suggesting that it occupied a similar binding site and inhibited viral replication in Vero-E6 cells, opening new design opportunities for further development as antiviral agents.
Keywords: SARS-CoV-2, drug repurposing, papain-like protease, redox, STD-NMR, CPI-169, GRL-0617
Published in DiRROS: 20.08.2025; Views: 768; Downloads: 517
Full text (1,73 MB)
This document has many files! More... |
