FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3184010507> ?p ?o ?g. }

• W3184010507 endingPage "1871" @default.
• W3184010507 startingPage "1871" @default.
• W3184010507 abstract "Alzheimer's disease (AD) is the most common neurodegenerative disorder and results in severe neurodegeneration and progressive cognitive decline. Neurotrophins are growth factors involved in the development and survival of neurons, but also in underlying mechanisms for memory formation such as hippocampal long-term potentiation. Our aim was to identify small molecules with stimulatory effects on the signaling of two neurotrophins, the nerve growth factor (NGF) and the brain derived neurotrophic factor (BDNF). To identify molecules that could potentiate neurotrophin signaling, 25,000 molecules were screened, which led to the identification of the triazinetrione derivatives ACD855 (Ponazuril) and later on ACD856, as positive allosteric modulators of tropomyosin related kinase (Trk) receptors. ACD855 or ACD856 potentiated the cellular signaling of the neurotrophin receptors with EC50 values of 1.9 and 3.2 or 0.38 and 0.30 µM, respectively, for TrkA or TrkB. ACD855 increased acetylcholine levels in the hippocampus by 40% and facilitated long term potentiation in rat brain slices. The compounds acted as cognitive enhancers in a TrkB-dependent manner in several different behavioral models. Finally, the age-induced cognitive dysfunction in 18-month-old mice could be restored to the same level as found in 2-month-old mice after a single treatment of ACD856. We have identified a novel mechanism to modulate the activity of the Trk-receptors. The identification of the positive allosteric modulators of the Trk-receptors might have implications for the treatment of Alzheimer's diseases and other diseases characterized by cognitive impairment." @default.
• W3184010507 created "2021-08-02" @default.
• W3184010507 creator A5000443883 @default.
• W3184010507 creator A5009248272 @default.
• W3184010507 creator A5012159562 @default.
• W3184010507 creator A5022769082 @default.
• W3184010507 creator A5028530566 @default.
• W3184010507 creator A5030049936 @default.
• W3184010507 creator A5030336367 @default.
• W3184010507 creator A5073068333 @default.
• W3184010507 creator A5081283156 @default.
• W3184010507 creator A5091613999 @default.
• W3184010507 date "2021-07-23" @default.
• W3184010507 modified "2023-10-17" @default.
• W3184010507 title "Identification of Novel Positive Allosteric Modulators of Neurotrophin Receptors for the Treatment of Cognitive Dysfunction" @default.
• W3184010507 cites W1527035699 @default.
• W3184010507 cites W1585500744 @default.
• W3184010507 cites W1964793927 @default.
• W3184010507 cites W1965289808 @default.
• W3184010507 cites W1971263143 @default.
• W3184010507 cites W1985729165 @default.
• W3184010507 cites W1987690978 @default.
• W3184010507 cites W1992410464 @default.
• W3184010507 cites W1995490147 @default.
• W3184010507 cites W1998751550 @default.
• W3184010507 cites W2001931352 @default.
• W3184010507 cites W2005889466 @default.
• W3184010507 cites W2006733352 @default.
• W3184010507 cites W2011789776 @default.
• W3184010507 cites W2012423618 @default.
• W3184010507 cites W2016992321 @default.
• W3184010507 cites W2022656029 @default.
• W3184010507 cites W2035061115 @default.
• W3184010507 cites W2044993609 @default.
• W3184010507 cites W2048515703 @default.
• W3184010507 cites W2050265432 @default.
• W3184010507 cites W2055583081 @default.
• W3184010507 cites W2058650902 @default.
• W3184010507 cites W2061117696 @default.
• W3184010507 cites W2067566555 @default.
• W3184010507 cites W2069312841 @default.
• W3184010507 cites W2071610467 @default.
• W3184010507 cites W2071852876 @default.
• W3184010507 cites W2072367004 @default.
• W3184010507 cites W2075117930 @default.
• W3184010507 cites W2079865565 @default.
• W3184010507 cites W2080638151 @default.
• W3184010507 cites W2080880626 @default.
• W3184010507 cites W2081599094 @default.
• W3184010507 cites W2083740224 @default.
• W3184010507 cites W2084865177 @default.
• W3184010507 cites W2086236480 @default.
• W3184010507 cites W2089454493 @default.
• W3184010507 cites W2091170554 @default.
• W3184010507 cites W2093045937 @default.
• W3184010507 cites W2099606443 @default.
• W3184010507 cites W2101258162 @default.
• W3184010507 cites W2119184935 @default.
• W3184010507 cites W2130417276 @default.
• W3184010507 cites W2130743873 @default.
• W3184010507 cites W2133482394 @default.
• W3184010507 cites W2133911179 @default.
• W3184010507 cites W2136761139 @default.
• W3184010507 cites W2137419542 @default.
• W3184010507 cites W2138009201 @default.
• W3184010507 cites W2140243281 @default.
• W3184010507 cites W2141650485 @default.
• W3184010507 cites W2166460033 @default.
• W3184010507 cites W2194077795 @default.
• W3184010507 cites W2329499411 @default.
• W3184010507 cites W2336783249 @default.
• W3184010507 cites W2441307729 @default.
• W3184010507 cites W2469782527 @default.
• W3184010507 cites W2482337617 @default.
• W3184010507 cites W2510233326 @default.
• W3184010507 cites W2520579003 @default.
• W3184010507 cites W2529170838 @default.
• W3184010507 cites W2543721277 @default.
• W3184010507 cites W2548660337 @default.
• W3184010507 cites W2580976313 @default.
• W3184010507 cites W2581545215 @default.
• W3184010507 cites W2610695657 @default.
• W3184010507 cites W2616456751 @default.
• W3184010507 cites W2752591735 @default.
• W3184010507 cites W2791053015 @default.
• W3184010507 cites W2801455203 @default.
• W3184010507 cites W2807524908 @default.
• W3184010507 cites W2912344221 @default.
• W3184010507 cites W2923160173 @default.
• W3184010507 cites W2957949878 @default.
• W3184010507 cites W2969831920 @default.
• W3184010507 cites W3132500005 @default.
• W3184010507 cites W3138811377 @default.
• W3184010507 cites W4230454755 @default.
• W3184010507 doi "https://doi.org/10.3390/cells10081871" @default.
• W3184010507 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8391421" @default.
• W3184010507 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34440640" @default.
• W3184010507 hasPublicationYear "2021" @default.

• next