E-viri
Recenzirano
Odprti dostop
-
Xu, Yun; Kong, Jiming; Hu, Pingzhao
Frontiers in pharmacology, 06/2021, Letnik: 12Journal Article
Background: Traditional therapeutics targeting Alzheimer’s disease (AD)-related subpathologies have so far proved ineffective. Drug repurposing, a more effective strategy that aims to find new indications for existing drugs against other diseases, offers benefits in AD drug development. In this study, we aim to identify potential anti-AD agents through enrichment analysis of drug-induced transcriptional profiles of pathways based on AD-associated risk genes identified from genome-wide association analyses (GWAS) and single-cell transcriptomic studies. Methods: We systematically constructed four gene lists (972 risk genes) from GWAS and single-cell transcriptomic studies and performed functional and genes overlap analyses in Enrichr tool. We then used a comprehensive drug repurposing tool Gene2Drug by combining drug-induced transcriptional responses with the associated pathways to compute candidate drugs from each gene list. Prioritized potential candidates (eight drugs) were further assessed with literature review. Results: The genomic-based gene lists contain late-onset AD associated genes (BIN1, ABCA7, APOE, CLU, and PICALM) and clinical AD drug targets (TREM2, CD33, CHRNA2, PRSS8, ACE, TKT, APP, and GABRA1). Our analysis identified eight AD candidate drugs (ellipticine, alsterpaullone, tomelukast, ginkgolide A, chrysin, ouabain, sulindac sulfide and lorglumide), four of which (alsterpaullone, ginkgolide A, chrysin and ouabain) have shown repurposing potential for AD validated by their preclinical evidence and moderate toxicity profiles from literature. These support the value of pathway-based prioritization based on the disease risk genes from GWAS and scRNA-seq data analysis. Conclusion: Our analysis strategy identified some potential drug candidates for AD. Although the drugs still need further experimental validation, the approach may be applied to repurpose drugs for other neurological disorders using their genomic information identified from large-scale genomic studies.
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.