GSE254742 Sildenafil as a candidate drug for Alzheimer ’s disease: Real-world patient data observation and mechanistic observations from patient-induced pluripotent stem cell-derived neurons.

Contributors : Dhruv Gohel ; Amit K Gupta ; Feixiong ChengSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensAlzheimer ’s disease (AD) is a chronic neurodegenerative disease needing effective therapeutics urgently. Sildenafil, one of the approved phosphodiesterase-5 inhibitors, has been implicated as having potential beneficial effect in AD. We showed that sildenafil usage is associated with reduced likelihood of AD across four new drug compactor cohorts, including bumetanide, furosemide, spironolactone, and nifedipine. For instance, sildenafil usage is associated with a 54% reduced prevalence of AD in MarketScan® (hazard ratio [HR] = 0.46, 95% CI 0.32-0.66) and a 30% reduced prevalence of AD in Clinformati cs® (HR = 0.70, 95% CI 0.49-1.00) compared to spironolactone. We found that sildenafil treatment significantly reduced tau hyper-phosphorylation (pTau181, pTau205) in a dose-dependent manner in both familial and sporadic AD patient derived neurons. Further RNA-seq data analysis of sildenafil-treate d AD patient iPSC-derived neurons revealed that sildenafil specifically targeting AD related genes and molecular pathways involved in axon guidance, AD-presenilin, neurogenesis, neurodegeneration, synaptic dysregulation, vascular smooth muscle contraction (VSMC) and cyclic guanosine monophosphate (c GMP)-protein kinase G (PKG) signaling pathway, mechanistically supporting the potential beneficial effect of sildenafil in AD. These real-wo...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research