Matches in SemOpenAlex for { <https://semopenalex.org/work/W3201911879> ?p ?o ?g. }
- W3201911879 endingPage "105516" @default.
- W3201911879 startingPage "105516" @default.
- W3201911879 abstract "Of the family of polyglutamine (polyQ) neurodegenerative diseases, Spinocerebellar Ataxia Type 3 (SCA3) is the most common. Like other polyQ diseases, SCA3 stems from abnormal expansions in the CAG triplet repeat of its disease gene resulting in elongated polyQ repeats within its protein, ataxin-3. Various ataxin-3 protein domains contribute to its toxicity, including the valosin-containing protein (VCP)-binding motif (VBM). We previously reported that VCP, a homo-hexameric protein, enhances pathogenic ataxin-3 aggregation and exacerbates its toxicity. These findings led us to explore the impact of targeting the SCA3 protein by utilizing a decoy protein comprising the N-terminus of VCP (N-VCP) that binds ataxin-3's VBM. The notion was that N-VCP would reduce binding of ataxin-3 to VCP, decreasing its aggregation and toxicity. We found that expression of N-VCP in Drosophila melanogaster models of SCA3 ameliorated various phenotypes, coincident with reduced ataxin-3 aggregation. This protective effect was specific to pathogenic ataxin-3 and depended on its VBM. Increasing the amount of N-VCP resulted in further phenotype improvement. Our work highlights the protective potential of targeting the VCP-ataxin-3 interaction in SCA3, a key finding in the search for therapeutic opportunities for this incurable disorder." @default.
- W3201911879 created "2021-10-11" @default.
- W3201911879 creator A5015630273 @default.
- W3201911879 creator A5015909717 @default.
- W3201911879 creator A5033658697 @default.
- W3201911879 creator A5038439202 @default.
- W3201911879 creator A5049739986 @default.
- W3201911879 creator A5059521824 @default.
- W3201911879 creator A5086545751 @default.
- W3201911879 date "2021-12-01" @default.
- W3201911879 modified "2023-10-16" @default.
- W3201911879 title "Targeting the VCP-binding motif of ataxin-3 improves phenotypes in Drosophila models of Spinocerebellar Ataxia Type 3" @default.
- W3201911879 cites W1180737757 @default.
- W3201911879 cites W140186299 @default.
- W3201911879 cites W1496748157 @default.
- W3201911879 cites W1511148913 @default.
- W3201911879 cites W1519439387 @default.
- W3201911879 cites W1531178007 @default.
- W3201911879 cites W1533943458 @default.
- W3201911879 cites W1594280279 @default.
- W3201911879 cites W1777831458 @default.
- W3201911879 cites W1892438599 @default.
- W3201911879 cites W1966882351 @default.
- W3201911879 cites W1969725515 @default.
- W3201911879 cites W1974031565 @default.
- W3201911879 cites W1974778184 @default.
- W3201911879 cites W1975403755 @default.
- W3201911879 cites W1975576680 @default.
- W3201911879 cites W1979964642 @default.
- W3201911879 cites W1980263472 @default.
- W3201911879 cites W1986865371 @default.
- W3201911879 cites W1988276706 @default.
- W3201911879 cites W1992436832 @default.
- W3201911879 cites W1997180807 @default.
- W3201911879 cites W2011343082 @default.
- W3201911879 cites W2018185396 @default.
- W3201911879 cites W2022486367 @default.
- W3201911879 cites W2024442371 @default.
- W3201911879 cites W2030985020 @default.
- W3201911879 cites W2031843296 @default.
- W3201911879 cites W2032459218 @default.
- W3201911879 cites W2034537895 @default.
- W3201911879 cites W2037008545 @default.
- W3201911879 cites W2042811939 @default.
- W3201911879 cites W2045373774 @default.
- W3201911879 cites W2046521227 @default.
- W3201911879 cites W2048600925 @default.
- W3201911879 cites W2057322261 @default.
- W3201911879 cites W2062203120 @default.
- W3201911879 cites W2063148128 @default.
- W3201911879 cites W2063608117 @default.
- W3201911879 cites W2068067496 @default.
- W3201911879 cites W2068244304 @default.
- W3201911879 cites W2068306128 @default.
- W3201911879 cites W2073012734 @default.
- W3201911879 cites W2074999466 @default.
- W3201911879 cites W2077292361 @default.
- W3201911879 cites W2079196169 @default.
- W3201911879 cites W2080378383 @default.
- W3201911879 cites W2083304341 @default.
- W3201911879 cites W2086085629 @default.
- W3201911879 cites W2086858480 @default.
- W3201911879 cites W2090054185 @default.
- W3201911879 cites W2104582907 @default.
- W3201911879 cites W2104692716 @default.
- W3201911879 cites W2116607997 @default.
- W3201911879 cites W2122353232 @default.
- W3201911879 cites W2124622589 @default.
- W3201911879 cites W2127706337 @default.
- W3201911879 cites W2131254563 @default.
- W3201911879 cites W2136095036 @default.
- W3201911879 cites W2136412949 @default.
- W3201911879 cites W2137546687 @default.
- W3201911879 cites W2141284487 @default.
- W3201911879 cites W2145141708 @default.
- W3201911879 cites W2146181664 @default.
- W3201911879 cites W2152351845 @default.
- W3201911879 cites W2160720083 @default.
- W3201911879 cites W2162194331 @default.
- W3201911879 cites W2162470793 @default.
- W3201911879 cites W2172574008 @default.
- W3201911879 cites W2337084848 @default.
- W3201911879 cites W239488127 @default.
- W3201911879 cites W2521135822 @default.
- W3201911879 cites W2537623931 @default.
- W3201911879 cites W2580352340 @default.
- W3201911879 cites W2585612456 @default.
- W3201911879 cites W2599425059 @default.
- W3201911879 cites W264011536 @default.
- W3201911879 cites W2747198643 @default.
- W3201911879 cites W2789586042 @default.
- W3201911879 cites W2802083987 @default.
- W3201911879 cites W2805986262 @default.
- W3201911879 cites W2810678568 @default.
- W3201911879 cites W2884379346 @default.
- W3201911879 cites W2887748872 @default.
- W3201911879 cites W2900512212 @default.
- W3201911879 cites W2900569176 @default.