Matches in SemOpenAlex for { <https://semopenalex.org/work/W4283700900> ?p ?o ?g. }
- W4283700900 endingPage "2234" @default.
- W4283700900 startingPage "2222" @default.
- W4283700900 abstract "Tauopathies are a class of neurodegenerative disorders characterized by the accumulation of tau protein filaments in the brain. On the basis of isoforms with three or four microtubule-binding repeats (3R or 4R) that constitute tau filaments, tauopathies can be divided into 3R, 4R, and 3R/4R tauopathies. [18F]PI-2620 is a tau-positron emission tomography (PET) tracer that detects tau filaments in the 3R/4R tauopathy Alzheimer's disease (AD) and the 4R tauopathies corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) with differential binding characteristics. A multiscale simulation workflow, including molecular docking, molecular dynamics simulation, metadynamics, and Brownian dynamics, was applied to uncover the molecular basis for the different binding properties of [18F]PI-2620 in these tauopathies. The energetically best binding sites of [18F]PI-2620 in the AD-tau filament are located in the C-shaped groove of the filament core structure that is accessible to the outside. The most favorable binding sites in CBD-tau and PSP-tau filaments are localized to cavities in the inner filament core. Sites on the outer surface have higher binding free energies, and interaction of [18F]PI-2620 at these sites was short-lived in the molecular dynamics simulations. Computationally predicted associated rates of [18F]PI-2620 with the groove sites in the AD-tau filament were higher than association rates with the cavity sites in the CBD- and PSP-tau filaments. The results indicate that tau filaments in AD combine favorable energetic and kinetic properties with regard to tracer binding, while the binding of [18F]PI-2620 to filaments in CBD and PSP is kinetically restricted. Our findings reveal that distinct structural, energetic, and kinetic properties of tau filaments from AD, CBD, and PSP govern their interaction with PET tracers, which highlights the possibility to achieve tau isoform specificity in future tracer developments." @default.
- W4283700900 created "2022-06-30" @default.
- W4283700900 creator A5008894116 @default.
- W4283700900 creator A5015382327 @default.
- W4283700900 creator A5034480643 @default.
- W4283700900 creator A5035814975 @default.
- W4283700900 creator A5047813770 @default.
- W4283700900 creator A5060633616 @default.
- W4283700900 creator A5085030601 @default.
- W4283700900 date "2022-06-28" @default.
- W4283700900 modified "2023-10-03" @default.
- W4283700900 title "Molecular Simulations Reveal Distinct Energetic and Kinetic Binding Properties of [<sup>18</sup>F]PI-2620 on Tau Filaments from 3R/4R and 4R Tauopathies" @default.
- W4283700900 cites W1024072833 @default.
- W4283700900 cites W1507887256 @default.
- W4283700900 cites W1509571186 @default.
- W4283700900 cites W1552029653 @default.
- W4283700900 cites W1902303720 @default.
- W4283700900 cites W1968984443 @default.
- W4283700900 cites W1969189143 @default.
- W4283700900 cites W1975580333 @default.
- W4283700900 cites W1977640602 @default.
- W4283700900 cites W1981021420 @default.
- W4283700900 cites W2003128923 @default.
- W4283700900 cites W2015688756 @default.
- W4283700900 cites W2016883591 @default.
- W4283700900 cites W2028046413 @default.
- W4283700900 cites W2029582401 @default.
- W4283700900 cites W2033350048 @default.
- W4283700900 cites W2057806291 @default.
- W4283700900 cites W2067174909 @default.
- W4283700900 cites W2084493621 @default.
- W4283700900 cites W2103591844 @default.
- W4283700900 cites W2103994532 @default.
- W4283700900 cites W2106140689 @default.
- W4283700900 cites W2123891429 @default.
- W4283700900 cites W2146411229 @default.
- W4283700900 cites W2147993766 @default.
- W4283700900 cites W2152903006 @default.
- W4283700900 cites W2159377066 @default.
- W4283700900 cites W2172650616 @default.
- W4283700900 cites W2219920450 @default.
- W4283700900 cites W2409859084 @default.
- W4283700900 cites W2590870875 @default.
- W4283700900 cites W2606439133 @default.
- W4283700900 cites W2727929522 @default.
- W4283700900 cites W2779391140 @default.
- W4283700900 cites W2791633767 @default.
- W4283700900 cites W2794217300 @default.
- W4283700900 cites W2796637563 @default.
- W4283700900 cites W2797441036 @default.
- W4283700900 cites W2891796239 @default.
- W4283700900 cites W2898161108 @default.
- W4283700900 cites W2923034350 @default.
- W4283700900 cites W2944245644 @default.
- W4283700900 cites W2954051589 @default.
- W4283700900 cites W2956696709 @default.
- W4283700900 cites W2984450782 @default.
- W4283700900 cites W2989052455 @default.
- W4283700900 cites W3005583156 @default.
- W4283700900 cites W3009011556 @default.
- W4283700900 cites W3038832112 @default.
- W4283700900 cites W3091614937 @default.
- W4283700900 cites W3096199793 @default.
- W4283700900 cites W3097325346 @default.
- W4283700900 cites W3136583108 @default.
- W4283700900 cites W3164358524 @default.
- W4283700900 cites W3164978586 @default.
- W4283700900 cites W3173913843 @default.
- W4283700900 cites W3193873334 @default.
- W4283700900 cites W3196899210 @default.
- W4283700900 cites W3202815206 @default.
- W4283700900 cites W3214868135 @default.
- W4283700900 cites W4211238543 @default.
- W4283700900 cites W4235092975 @default.
- W4283700900 doi "https://doi.org/10.1021/acschemneuro.2c00291" @default.
- W4283700900 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35762647" @default.
- W4283700900 hasPublicationYear "2022" @default.
- W4283700900 type Work @default.
- W4283700900 citedByCount "9" @default.
- W4283700900 countsByYear W42837009002023 @default.
- W4283700900 crossrefType "journal-article" @default.
- W4283700900 hasAuthorship W4283700900A5008894116 @default.
- W4283700900 hasAuthorship W4283700900A5015382327 @default.
- W4283700900 hasAuthorship W4283700900A5034480643 @default.
- W4283700900 hasAuthorship W4283700900A5035814975 @default.
- W4283700900 hasAuthorship W4283700900A5047813770 @default.
- W4283700900 hasAuthorship W4283700900A5060633616 @default.
- W4283700900 hasAuthorship W4283700900A5085030601 @default.
- W4283700900 hasConcept C107824862 @default.
- W4283700900 hasConcept C12554922 @default.
- W4283700900 hasConcept C14228908 @default.
- W4283700900 hasConcept C142724271 @default.
- W4283700900 hasConcept C147597530 @default.
- W4283700900 hasConcept C170493617 @default.
- W4283700900 hasConcept C185592680 @default.
- W4283700900 hasConcept C2776477761 @default.
- W4283700900 hasConcept C2776925932 @default.
- W4283700900 hasConcept C2776936178 @default.