Identification of Novel Positive Allosteric Modulators of Neurotrophin Receptors for the Treatment of Cognitive Dysfunction.
Age Factors
Animals
Behavior, Animal
/ drug effects
Brain
/ drug effects
Cell Line, Tumor
Cognition
/ drug effects
Cognitive Dysfunction
/ drug therapy
Disease Models, Animal
Humans
Male
Maze Learning
/ drug effects
Membrane Glycoproteins
Mice, Inbred C57BL
Motor Activity
/ drug effects
Nootropic Agents
/ pharmacology
Protein-Tyrosine Kinases
Rats, Sprague-Dawley
Receptor, trkA
/ agonists
Receptor, trkB
/ agonists
Receptors, Nerve Growth Factor
/ agonists
Signal Transduction
Small Molecule Libraries
Triazines
/ pharmacology
Alzheimer’s disease
TrkA
TrkB
brain derived neurotrophic factor
cognition
nerve growth factor
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
23 07 2021
23 07 2021
Historique:
received:
22
06
2021
revised:
16
07
2021
accepted:
19
07
2021
entrez:
27
8
2021
pubmed:
28
8
2021
medline:
16
11
2021
Statut:
epublish
Résumé
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 EC
Identifiants
pubmed: 34440640
pii: cells10081871
doi: 10.3390/cells10081871
pmc: PMC8391421
pii:
doi:
Substances chimiques
Membrane Glycoproteins
0
NTRK1 protein, human
0
Nootropic Agents
0
Receptors, Nerve Growth Factor
0
Small Molecule Libraries
0
Triazines
0
Ntrk2 protein, mouse
EC 2.7.10.1
Ntrk2 protein, rat
EC 2.7.10.1
Protein-Tyrosine Kinases
EC 2.7.10.1
Receptor, trkA
EC 2.7.10.1
Receptor, trkB
EC 2.7.10.1
tropomyosin-related kinase-B, human
EC 2.7.10.1
ponazuril
JPW84AS66U
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Alzheimer's Drug Discovery Foundation
ID : 20151003
Organisme : VINNOVA
ID : 2014-00347
Références
Eur Heart J. 2013 Sep;34(33):2585-91
pubmed: 23735859
Neurobiol Aging. 2013 Nov;34(11):2457-64
pubmed: 23769397
Neurology. 2021 Apr 27;96(17):e2220-e2230
pubmed: 33741639
CNS Neurol Disord Drug Targets. 2011 Aug;10(5):635-47
pubmed: 21631402
Proc Natl Acad Sci U S A. 1990 Jul;87(14):5454-8
pubmed: 2164684
Nat Neurosci. 2010 Mar;13(3):302-9
pubmed: 20173744
Neurobiol Aging. 2012 Jun;33(6):1122.e23-39
pubmed: 22209410
Brain Res. 2015 Sep 24;1621:82-101
pubmed: 25451089
Alzheimers Dement. 2015 Nov;11(11):1316-28
pubmed: 25676388
J Biomed Sci. 2015 Dec 08;22:106
pubmed: 26642930
J Biomol Screen. 2013 Jul;18(6):659-69
pubmed: 23458757
Science. 1990 Mar 23;247(4949 Pt 1):1446-51
pubmed: 2321006
J Med Chem. 2002 Sep 26;45(20):4387-90
pubmed: 12238916
J Biol Chem. 2000 Sep 22;275(38):29868-74
pubmed: 10896671
Nat Med. 2009 Mar;15(3):331-7
pubmed: 19198615
Behav Neurosci. 2002 Jun;116(3):455-63
pubmed: 12049326
Ann N Y Acad Sci. 1952 Aug 8;55(2):330-44
pubmed: 12977049
Transl Psychiatry. 2016 Oct 4;6(10):e907
pubmed: 27701410
Neuron. 1991 Nov;7(5):857-66
pubmed: 1742028
J Neurosci Methods. 1998 Sep 1;83(2):143-50
pubmed: 9765127
Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16329-34
pubmed: 17911251
Eur J Neurosci. 2019 Nov;50(9):3487-3501
pubmed: 31301255
Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2687-92
pubmed: 20133810
Parasitol Res. 1988;75(1):64-6
pubmed: 3144713
Neurobiol Dis. 2008 Sep;31(3):316-26
pubmed: 18585459
Brain. 2016 Oct;139(Pt 10):2766-2777
pubmed: 27521573
Life Sci. 2003 Jun 20;73(5):539-53
pubmed: 12770610
J Neurosci. 2008 Mar 12;28(11):2698-709
pubmed: 18337399
Alzheimers Res Ther. 2016 Jul 07;8(1):30
pubmed: 27389402
Alzheimers Dement. 2018 Jul;14(7):944-951
pubmed: 29706487
Cell. 2021 Mar 4;184(5):1299-1313.e19
pubmed: 33606976
J Vet Pharmacol Ther. 2014 Dec;37(6):598-602
pubmed: 24731142
Neuron. 1999 Oct;24(2):401-14
pubmed: 10571233
Neurology. 2017 May 30;88(22):2098-2106
pubmed: 28468845
Drug Des Devel Ther. 2016 Nov 02;10:3545-3553
pubmed: 27843294
Expert Rev Neurother. 2012 Nov;12(11):1351-65
pubmed: 23234396
Learn Mem. 2008 Aug 26;15(9):625-32
pubmed: 18772249
Ann Neurol. 2004 Oct;56(4):520-31
pubmed: 15455399
J Clin Invest. 2010 May;120(5):1774-85
pubmed: 20407211
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Jan 1;845(1):109-13
pubmed: 16979391
Learn Mem. 2004 Jan-Feb;11(1):43-9
pubmed: 14747516
Chem Biol. 2009 Jun 26;16(6):644-56
pubmed: 19549602
J Vis Exp. 2017 Aug 30;(126):
pubmed: 28892027
Neuropharmacology. 2017 Feb;113(Pt A):100-109
pubmed: 27470063
Dement Geriatr Cogn Disord. 2012;33(1):18-28
pubmed: 22377499
Front Mol Neurosci. 2017 Jan 31;10:15
pubmed: 28197073
Eur J Clin Pharmacol. 2019 Dec;75(12):1659-1667
pubmed: 31435707
J Pharmacol Exp Ther. 2006 Feb;316(2):581-91
pubmed: 16223872
Neural Regen Res. 2016 Oct;11(10):1553-1556
pubmed: 27904476
EMBO J. 1982;1(5):549-53
pubmed: 7188352
J Pharmacol Exp Ther. 2007 Jul;322(1):59-69
pubmed: 17468299
J Antibiot (Tokyo). 1999 Mar;52(3):224-30
pubmed: 10348036
Mol Pharmacol. 2000 Feb;57(2):385-91
pubmed: 10648649
Eur J Neurosci. 2002 Jul;16(1):145-8
pubmed: 12153539
Eur J Neurosci. 1997 Dec;9(12):2581-7
pubmed: 9517463
J Vet Pharmacol Ther. 2009 Jun;32(3):280-8
pubmed: 19646093
Ann Clin Microbiol Antimicrob. 2002 Oct 18;1:4
pubmed: 12437777
Neurobiol Aging. 2017 May;53:192.e11-192.e19
pubmed: 28202203
Vet Ther. 2001 Summer;2(3):215-22
pubmed: 19746664
Front Neurosci. 2019 Feb 05;13:38
pubmed: 30804738
Lab Anim. 1983 Jan;17(1):59-64
pubmed: 6865312
Mol Cell Neurosci. 2003 Nov;24(3):568-80
pubmed: 14664808
Cell Death Differ. 2013 Aug;20(8):1017-30
pubmed: 23538417
Alzheimers Dement (N Y). 2017 May 17;3(3):402-409
pubmed: 29067346
Mol Psychiatry. 2021 Feb;26(2):614-628
pubmed: 30899092
Cell Death Dis. 2012 Jul 05;3:e339
pubmed: 22764098
Hippocampus. 2002;12(4):551-60
pubmed: 12201640
Acta Vet Scand. 1986;27(1):124-37
pubmed: 3751809
Front Mol Neurosci. 2018 Feb 22;11:51
pubmed: 29520217
Neuropharmacology. 2016 Dec;111:266-282
pubmed: 27618740
Behav Brain Res. 2014 Sep 1;271:309-15
pubmed: 24946073
J Am Geriatr Soc. 2018 Sep;66(9):1805-1811
pubmed: 29851022
Cell. 2003 Jan 24;112(2):257-69
pubmed: 12553913
J Neurochem. 2001 Sep;78(5):1135-45
pubmed: 11553687
Nat Rev Neurosci. 2003 Apr;4(4):299-309
pubmed: 12671646
J Antibiot (Tokyo). 1992 Oct;45(10):1566-72
pubmed: 1473983
Exp Eye Res. 2011 Oct;93(4):503-12
pubmed: 21726552
Vet Ther. 2001 Summer;2(3):223-31
pubmed: 19746665
Nature. 1996 Jun 20;381(6584):706-9
pubmed: 8649517
J Neurosci Methods. 2004 Dec 30;140(1-2):163-8
pubmed: 15589346
J Biol Chem. 1995 Mar 24;270(12):6564-9
pubmed: 7896793
Aging Cell. 2016 Aug;15(4):661-72
pubmed: 27076121