FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2040646197> ?p ?o ?g. }

• W2040646197 endingPage "61" @default.
• W2040646197 startingPage "49" @default.
• W2040646197 abstract "Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant Parkinson's disease (PD). LRRK2 contains functional GTPase and kinase domains. The most common G2019S mutation enhances the kinase activity of LRRK2 in vitro whereas G2019S LRRK2 expression in cultured neurons induces toxicity in a kinase-dependent manner. These observations suggest a potential role for kinase activity in LRRK2-associated PD. We have recently developed a novel rodent model of PD with progressive neurodegeneration induced by the adenoviral-mediated expression of G2019S LRRK2. In the present study, we further characterize this LRRK2 model and determine the contribution of kinase activity to LRRK2-mediated neurodegeneration. Recombinant human adenoviral vectors were employed to deliver human wild-type, G2019S or kinase-inactive G2019S/D1994N LRRK2 to the rat striatum. LRRK2-dependent pathology was assessed in the striatum, a region where LRRK2 protein is normally enriched in the mammalian brain. Human LRRK2 variants are robustly expressed throughout the rat striatum. Expression of G2019S LRRK2 selectively induces the accumulation of neuronal ubiquitin-positive inclusions accompanied by neurite degeneration and the altered distribution of axonal phosphorylated neurofilaments. Importantly, the introduction of a kinase-inactive mutation (G2019S/D1994N) completely ameliorates the pathological effects of G2019S LRRK2 in the striatum supporting a kinase activity-dependent mechanism for this PD-associated mutation. Collectively, our study further elucidates the pathological effects of the G2019S mutation in the mammalian brain and supports the development of kinase inhibitors as a potential therapeutic approach for treating LRRK2-associated PD. This adenoviral rodent model provides an important tool for elucidating the molecular basis of LRRK2-mediated neurodegeneration." @default.
• W2040646197 created "2016-06-24" @default.
• W2040646197 creator A5000792302 @default.
• W2040646197 creator A5015073187 @default.
• W2040646197 creator A5037205059 @default.
• W2040646197 creator A5068434961 @default.
• W2040646197 creator A5070964840 @default.
• W2040646197 creator A5079137532 @default.
• W2040646197 date "2015-05-01" @default.
• W2040646197 modified "2023-10-01" @default.
• W2040646197 title "Adenoviral-mediated expression of G2019S LRRK2 induces striatal pathology in a kinase-dependent manner in a rat model of Parkinson's disease" @default.
• W2040646197 cites W1496790952 @default.
• W2040646197 cites W1527671059 @default.
• W2040646197 cites W1583371287 @default.
• W2040646197 cites W1967900265 @default.
• W2040646197 cites W1969997447 @default.
• W2040646197 cites W1972308707 @default.
• W2040646197 cites W1975194767 @default.
• W2040646197 cites W1977767269 @default.
• W2040646197 cites W1978419085 @default.
• W2040646197 cites W1983126354 @default.
• W2040646197 cites W1986961354 @default.
• W2040646197 cites W1991732882 @default.
• W2040646197 cites W1992365739 @default.
• W2040646197 cites W1993275163 @default.
• W2040646197 cites W2003883601 @default.
• W2040646197 cites W2006875797 @default.
• W2040646197 cites W2007404476 @default.
• W2040646197 cites W2013473672 @default.
• W2040646197 cites W2015784694 @default.
• W2040646197 cites W2019006980 @default.
• W2040646197 cites W2021209363 @default.
• W2040646197 cites W2022446710 @default.
• W2040646197 cites W2028171714 @default.
• W2040646197 cites W2028300828 @default.
• W2040646197 cites W2028796406 @default.
• W2040646197 cites W2032481706 @default.
• W2040646197 cites W2033485203 @default.
• W2040646197 cites W2045402408 @default.
• W2040646197 cites W2045728621 @default.
• W2040646197 cites W2046623850 @default.
• W2040646197 cites W2047565527 @default.
• W2040646197 cites W2050310121 @default.
• W2040646197 cites W2055927110 @default.
• W2040646197 cites W2056103666 @default.
• W2040646197 cites W2059514738 @default.
• W2040646197 cites W2063127941 @default.
• W2040646197 cites W2064379301 @default.
• W2040646197 cites W2068666140 @default.
• W2040646197 cites W2073922747 @default.
• W2040646197 cites W2082214922 @default.
• W2040646197 cites W2082471010 @default.
• W2040646197 cites W2087360216 @default.
• W2040646197 cites W2091654078 @default.
• W2040646197 cites W2095338669 @default.
• W2040646197 cites W2096905204 @default.
• W2040646197 cites W2100300726 @default.
• W2040646197 cites W2100894616 @default.
• W2040646197 cites W2103454698 @default.
• W2040646197 cites W2110439430 @default.
• W2040646197 cites W2112286366 @default.
• W2040646197 cites W2120262230 @default.
• W2040646197 cites W2121346405 @default.
• W2040646197 cites W2122072833 @default.
• W2040646197 cites W2124681346 @default.
• W2040646197 cites W2133207125 @default.
• W2040646197 cites W2134829539 @default.
• W2040646197 cites W2135947516 @default.
• W2040646197 cites W2136216054 @default.
• W2040646197 cites W2136314817 @default.
• W2040646197 cites W2146090441 @default.
• W2040646197 cites W2146890924 @default.
• W2040646197 cites W2148641246 @default.
• W2040646197 cites W2149224225 @default.
• W2040646197 cites W2152874097 @default.
• W2040646197 cites W2156959507 @default.
• W2040646197 cites W2160484806 @default.
• W2040646197 cites W2164778558 @default.
• W2040646197 cites W2166593844 @default.
• W2040646197 cites W2173140585 @default.
• W2040646197 cites W2573367782 @default.
• W2040646197 doi "https://doi.org/10.1016/j.nbd.2015.02.019" @default.
• W2040646197 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25731749" @default.
• W2040646197 hasPublicationYear "2015" @default.
• W2040646197 type Work @default.
• W2040646197 sameAs 2040646197 @default.
• W2040646197 citedByCount "43" @default.
• W2040646197 countsByYear W20406461972015 @default.
• W2040646197 countsByYear W20406461972016 @default.
• W2040646197 countsByYear W20406461972017 @default.
• W2040646197 countsByYear W20406461972018 @default.
• W2040646197 countsByYear W20406461972019 @default.
• W2040646197 countsByYear W20406461972020 @default.
• W2040646197 countsByYear W20406461972021 @default.
• W2040646197 countsByYear W20406461972022 @default.
• W2040646197 countsByYear W20406461972023 @default.
• W2040646197 crossrefType "journal-article" @default.
• W2040646197 hasAuthorship W2040646197A5000792302 @default.

• next