FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3195780314> ?p ?o ?g. }

• W3195780314 endingPage "261" @default.
• W3195780314 startingPage "244" @default.
• W3195780314 abstract "The purpose of our study is to understand the protective effects of small molecule ligands for phosphorylated tau (p-tau) in Alzheimer's disease (AD) progression. Many reports show evidence that phosphorylated tau is reported to be an important contributor to the formation of paired helical filaments (PHFs) and neurofibrillary tangles (NFTs) in AD neurons. In AD, glycogen synthase kinase-3 beta (GSK3β), cyclin-dependent kinase-5 and dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), are the three important kinases responsible for tau hyperphosphorylation. Currently, there are no drugs and/or small molecules that reduce the toxicity of phosphorylated tau in AD. In the present study, we rationally selected and validated small molecule ligands that bind to the phosphorylated tau at SER23 (Ser 285) and TYR44 (Tyr310). We also assessed the molecular dynamics and validated molecular docking sites for the three best ligands. Based on the best docking scores -8.09, -7.9 and -7.8 kcal/mol, we found that ligand 1 binds to key hyperphosphorylation residues of phosphorylated tau that inhibit abnormal PHF-tau, DYRK1A and GKS3β that reduce phosphorylated tau levels in AD. Using biochemical, molecular, immunoblotting, immunofluorescence and transmission electron microscopy analyses, we studied the ligand 1 inhibition as well as mitochondrial and synaptic protective effects in immortalized primary hippocampal neuronal (HT22) cells. We found interactions between NAT10-262501 (ligand 1) and phosphorylated tau at key phosphorylation sites and these ligand-based inhibitions decreased PHF-tau, DYRK1A and GSK3β levels. We also found increased mitochondrial biogenesis, mitochondrial fusion and synaptic activities and reduced mitochondrial fission in ligand 1-treated mutant tau HT22 cells. Based on these results, we cautiously conclude that phosphorylated tau NAT10-262501 (ligand 1) reduces hyperphosphorylation of tau based GKS3β and CDK5 kinase regulation in AD, and aids in the maintenance of neuronal structure, mitochondrial dynamics and biogenesis with a possible therapeutic drug target for AD." @default.
• W3195780314 created "2021-08-30" @default.
• W3195780314 creator A5032668464 @default.
• W3195780314 creator A5039684215 @default.
• W3195780314 creator A5042058638 @default.
• W3195780314 creator A5084673116 @default.
• W3195780314 date "2021-09-09" @default.
• W3195780314 modified "2023-10-17" @default.
• W3195780314 title "Protective effects of a small molecule inhibitor ligand against hyperphosphorylated tau-induced mitochondrial and synaptic toxicities in Alzheimer disease" @default.
• W3195780314 cites W1494495256 @default.
• W3195780314 cites W1608240838 @default.
• W3195780314 cites W1743841615 @default.
• W3195780314 cites W1830376997 @default.
• W3195780314 cites W1831651395 @default.
• W3195780314 cites W1841303832 @default.
• W3195780314 cites W1913159090 @default.
• W3195780314 cites W1963836683 @default.
• W3195780314 cites W1971468364 @default.
• W3195780314 cites W1988332799 @default.
• W3195780314 cites W1988477436 @default.
• W3195780314 cites W1989790854 @default.
• W3195780314 cites W1992830187 @default.
• W3195780314 cites W2007124162 @default.
• W3195780314 cites W2010515612 @default.
• W3195780314 cites W2011253324 @default.
• W3195780314 cites W2013308243 @default.
• W3195780314 cites W2026620570 @default.
• W3195780314 cites W2038026046 @default.
• W3195780314 cites W2042643712 @default.
• W3195780314 cites W2051034720 @default.
• W3195780314 cites W2051603499 @default.
• W3195780314 cites W2054223500 @default.
• W3195780314 cites W2054619408 @default.
• W3195780314 cites W2055116915 @default.
• W3195780314 cites W2060079863 @default.
• W3195780314 cites W2077332797 @default.
• W3195780314 cites W2078163062 @default.
• W3195780314 cites W2079766520 @default.
• W3195780314 cites W2082905363 @default.
• W3195780314 cites W2085782370 @default.
• W3195780314 cites W2091857357 @default.
• W3195780314 cites W2099795098 @default.
• W3195780314 cites W2125851351 @default.
• W3195780314 cites W2136750984 @default.
• W3195780314 cites W2141490098 @default.
• W3195780314 cites W2142366168 @default.
• W3195780314 cites W2143829202 @default.
• W3195780314 cites W2152188588 @default.
• W3195780314 cites W2331978208 @default.
• W3195780314 cites W2396911249 @default.
• W3195780314 cites W2398201425 @default.
• W3195780314 cites W2466841141 @default.
• W3195780314 cites W2517653272 @default.
• W3195780314 cites W2518762064 @default.
• W3195780314 cites W2605036205 @default.
• W3195780314 cites W2625356606 @default.
• W3195780314 cites W2737962827 @default.
• W3195780314 cites W2789405288 @default.
• W3195780314 cites W2792694489 @default.
• W3195780314 cites W2795794839 @default.
• W3195780314 cites W2802911313 @default.
• W3195780314 cites W2806598719 @default.
• W3195780314 cites W2810998522 @default.
• W3195780314 cites W2900998599 @default.
• W3195780314 cites W2924290921 @default.
• W3195780314 cites W2944031601 @default.
• W3195780314 cites W2945779890 @default.
• W3195780314 cites W2956696709 @default.
• W3195780314 cites W2984270613 @default.
• W3195780314 cites W3014542096 @default.
• W3195780314 cites W3019078121 @default.
• W3195780314 cites W3036201149 @default.
• W3195780314 cites W3087394043 @default.
• W3195780314 cites W3094335331 @default.
• W3195780314 cites W3128132069 @default.
• W3195780314 cites W3132629798 @default.
• W3195780314 cites W3156519105 @default.
• W3195780314 cites W3158856741 @default.
• W3195780314 cites W3166313369 @default.
• W3195780314 cites W4231781955 @default.
• W3195780314 doi "https://doi.org/10.1093/hmg/ddab244" @default.
• W3195780314 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34432046" @default.
• W3195780314 hasPublicationYear "2021" @default.
• W3195780314 type Work @default.
• W3195780314 sameAs 3195780314 @default.
• W3195780314 citedByCount "13" @default.
• W3195780314 countsByYear W31957803142021 @default.
• W3195780314 countsByYear W31957803142022 @default.
• W3195780314 countsByYear W31957803142023 @default.
• W3195780314 crossrefType "journal-article" @default.
• W3195780314 hasAuthorship W3195780314A5032668464 @default.
• W3195780314 hasAuthorship W3195780314A5039684215 @default.
• W3195780314 hasAuthorship W3195780314A5042058638 @default.
• W3195780314 hasAuthorship W3195780314A5084673116 @default.
• W3195780314 hasBestOaLocation W31957803142 @default.
• W3195780314 hasConcept C104629339 @default.
• W3195780314 hasConcept C11960822 @default.
• W3195780314 hasConcept C121738310 @default.

• next