Matches in SemOpenAlex for { <https://semopenalex.org/work/W2041941298> ?p ?o ?g. }
- W2041941298 endingPage "3306" @default.
- W2041941298 startingPage "3295" @default.
- W2041941298 abstract "Botulinum neurotoxins (BoNTs) are zinc endopeptidases that block release of the neurotransmitter acetylcholine in neuromuscular synapses through cleavage of soluble N-ethylmaleimide-sensitive fusion (NSF) attachment protein receptor (SNARE) proteins, which promote fusion of synaptic vesicles to the plasma membrane. We designed and tested a BoNT-derived targeted secretion inhibitor (TSI) targeting pituitary somatotroph cells to suppress growth hormone (GH) secretion and treat acromegaly. This recombinant protein, called SXN101742, contains a modified GH-releasing hormone (GHRH) domain and the endopeptidase domain of botulinum toxin serotype D (GHRH-LHN/D, where HN/D indicates endopeptidase and translocation domain type D). In vitro, SXN101742 targeted the GHRH receptor and depleted a SNARE protein involved in GH exocytosis, vesicle-associated membrane protein 2 (VAMP2). In vivo, administering SXN101742 to growing rats produced a dose-dependent inhibition of GH synthesis, storage, and secretion. Consequently, hepatic IGF1 production and resultant circulating IGF1 levels were reduced. Accordingly, body weight, body length, organ weight, and bone mass acquisition were all decreased, reflecting the biological impact of SXN101742 on the GH/IGF1 axis. An inactivating 2–amino acid substitution within the zinc coordination site of the endopeptidase domain completely abolished SXN101742 inhibitory actions on GH and IGF1. Thus, genetically reengineered BoNTs can be targeted to nonneural cells to selectively inhibit hormone secretion, representing a new approach to treating hormonal excess." @default.
- W2041941298 created "2016-06-24" @default.
- W2041941298 creator A5011735451 @default.
- W2041941298 creator A5013663301 @default.
- W2041941298 creator A5015169934 @default.
- W2041941298 creator A5019178175 @default.
- W2041941298 creator A5023356054 @default.
- W2041941298 creator A5023389415 @default.
- W2041941298 creator A5024094411 @default.
- W2041941298 creator A5037117397 @default.
- W2041941298 creator A5040345896 @default.
- W2041941298 creator A5043413597 @default.
- W2041941298 creator A5057557737 @default.
- W2041941298 creator A5066985276 @default.
- W2041941298 creator A5082866696 @default.
- W2041941298 creator A5084831116 @default.
- W2041941298 date "2012-09-04" @default.
- W2041941298 modified "2023-10-15" @default.
- W2041941298 title "A botulinum toxin–derived targeted secretion inhibitor downregulates the GH/IGF1 axis" @default.
- W2041941298 cites W123434114 @default.
- W2041941298 cites W1963573377 @default.
- W2041941298 cites W1964681883 @default.
- W2041941298 cites W1966977321 @default.
- W2041941298 cites W1967083598 @default.
- W2041941298 cites W1972196325 @default.
- W2041941298 cites W1975381297 @default.
- W2041941298 cites W1978614075 @default.
- W2041941298 cites W1980782637 @default.
- W2041941298 cites W1982185698 @default.
- W2041941298 cites W1986679235 @default.
- W2041941298 cites W1992460009 @default.
- W2041941298 cites W1999801514 @default.
- W2041941298 cites W2001597155 @default.
- W2041941298 cites W2003548488 @default.
- W2041941298 cites W2003607836 @default.
- W2041941298 cites W2008681136 @default.
- W2041941298 cites W2009111528 @default.
- W2041941298 cites W2025658717 @default.
- W2041941298 cites W2033646733 @default.
- W2041941298 cites W2035451060 @default.
- W2041941298 cites W2052918979 @default.
- W2041941298 cites W2058353252 @default.
- W2041941298 cites W2059027605 @default.
- W2041941298 cites W2060098417 @default.
- W2041941298 cites W2063981139 @default.
- W2041941298 cites W2065675161 @default.
- W2041941298 cites W2069561445 @default.
- W2041941298 cites W2077940121 @default.
- W2041941298 cites W2078541439 @default.
- W2041941298 cites W2080590083 @default.
- W2041941298 cites W2084732252 @default.
- W2041941298 cites W2084999017 @default.
- W2041941298 cites W2087235646 @default.
- W2041941298 cites W2093663819 @default.
- W2041941298 cites W2095591038 @default.
- W2041941298 cites W2097502952 @default.
- W2041941298 cites W2111894013 @default.
- W2041941298 cites W2113464653 @default.
- W2041941298 cites W2116623369 @default.
- W2041941298 cites W2123182986 @default.
- W2041941298 cites W2124230840 @default.
- W2041941298 cites W2127573768 @default.
- W2041941298 cites W2130967893 @default.
- W2041941298 cites W2131653836 @default.
- W2041941298 cites W2132834341 @default.
- W2041941298 cites W2149985387 @default.
- W2041941298 cites W2153200944 @default.
- W2041941298 cites W2153821490 @default.
- W2041941298 cites W2156136676 @default.
- W2041941298 cites W2159303404 @default.
- W2041941298 cites W2159967545 @default.
- W2041941298 cites W2160463128 @default.
- W2041941298 cites W2167481964 @default.
- W2041941298 cites W2168171339 @default.
- W2041941298 cites W2168239813 @default.
- W2041941298 cites W2170170331 @default.
- W2041941298 cites W2256257390 @default.
- W2041941298 cites W2320296534 @default.
- W2041941298 cites W2334565854 @default.
- W2041941298 cites W4234010107 @default.
- W2041941298 cites W4237353209 @default.
- W2041941298 cites W4238095656 @default.
- W2041941298 cites W4251646067 @default.
- W2041941298 cites W4254508296 @default.
- W2041941298 doi "https://doi.org/10.1172/jci63232" @default.
- W2041941298 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3428092" @default.
- W2041941298 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22850878" @default.
- W2041941298 hasPublicationYear "2012" @default.
- W2041941298 type Work @default.
- W2041941298 sameAs 2041941298 @default.
- W2041941298 citedByCount "55" @default.
- W2041941298 countsByYear W20419412982012 @default.
- W2041941298 countsByYear W20419412982013 @default.
- W2041941298 countsByYear W20419412982014 @default.
- W2041941298 countsByYear W20419412982015 @default.
- W2041941298 countsByYear W20419412982016 @default.
- W2041941298 countsByYear W20419412982017 @default.
- W2041941298 countsByYear W20419412982018 @default.