Substrate-selective positive allosteric modulation of PTPRD's phosphatase by flavonols.
Alzheimer’s disease
Glycogen synthase kinase 3
Neurodegeneration
Neurofibrillary tangles
Quercetin
Receptor type protein tyrosine phosphatase
Tauopathy
Journal
Biochemical pharmacology
ISSN: 1873-2968
Titre abrégé: Biochem Pharmacol
Pays: England
ID NLM: 0101032
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
12
03
2022
revised:
23
05
2022
accepted:
23
05
2022
pubmed:
1
6
2022
medline:
15
7
2022
entrez:
31
5
2022
Statut:
ppublish
Résumé
The receptor type protein tyrosine phosphatase D (PTPRD) is expressed by neurons and implicated in interesting phenotypes that include reward from addictive substances, restless leg syndrome and neurofibrillary tangle densities in Alzheimer's disease (AD-NFTs). However, the brain phosphotyrosine phosphoprotein (PTPP) substrates for PTPRD's phosphatase have not been clearly defined. Although we have identified small molecule inhibitors of PTPRD's phosphatase that are candidates for reducing reward from addictive substances, no positive allosteric modulators of this phosphatase that might be candidates for reducing AD-NFTs have been reported. We now report identification of candidate brain substrates for PTPRD based on their increased phosphorylation in knockout vs wildtype animals, coexpression with PTPRD in neuronal subtypes and brisk dephosphorylation by recombinant human PTPRD phosphatase. We also report discovery that quercetin and other flavonols, though not closely-related flavones, enhance rates of PTPRD's dephosphorylation of a group of these candidate substrate PTPPs but not others. This substrate-selective positive allosteric modulation provides a novel pharmacological action. Flavonol-mediated increases in PTPRD's dephosphorylation of the GSK3 β and α kinases that hyperphosphorylate tau, the major component of AD-NFTs, could help to explain recent data concerning genetic and dietary impacts on Alzheimer's disease.
Identifiants
pubmed: 35636503
pii: S0006-2952(22)00203-9
doi: 10.1016/j.bcp.2022.115109
pmc: PMC10184881
mid: NIHMS1815891
pii:
doi:
Substances chimiques
Flavonols
0
tau Proteins
0
Glycogen Synthase Kinase 3
EC 2.7.11.26
Phosphoric Monoester Hydrolases
EC 3.1.3.2
PTPRD protein, human
EC 3.1.3.48
Receptor-Like Protein Tyrosine Phosphatases, Class 2
EC 3.1.3.48
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
115109Subventions
Organisme : NIDA NIH HHS
ID : U01 DA047713
Pays : United States
Organisme : NIDA NIH HHS
ID : UG3 DA056039
Pays : United States
Informations de copyright
Published by Elsevier Inc.
Références
Neuroreport. 2016 Jun 15;27(9):671-6
pubmed: 27145228
Mol Med. 2015 Nov;21(1):717-725
pubmed: 26181631
J Comput Aided Mol Des. 2013 Mar;27(3):221-34
pubmed: 23579614
Neurobiol Aging. 2011 Jul;32(7):1249-61
pubmed: 19700222
Brain Res. 2016 Jul 1;1642:244-254
pubmed: 27026654
J Exp Med. 2005 Feb 7;201(3):441-52
pubmed: 15684325
Eur J Epidemiol. 2000 Apr;16(4):357-63
pubmed: 10959944
Anal Biochem. 1993 May 15;211(1):50-4
pubmed: 8323038
Mol Psychiatry. 2018 Jun;23(6):1521-1529
pubmed: 28322283
Am J Geriatr Psychiatry. 2010 May;18(5):413-20
pubmed: 19910881
Neurology. 2020 Apr 21;94(16):e1749-e1756
pubmed: 31996451
Aging Cell. 2019 Feb;18(1):e12873
pubmed: 30488653
Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):11597-11602
pubmed: 30348770
J Med Chem. 2006 Oct 19;49(21):6177-96
pubmed: 17034125
PLoS One. 2011 Apr 29;6(4):e18934
pubmed: 21572516
J Immunol. 2015 Mar 1;194(5):2168-79
pubmed: 25624455
Molecules. 2019 Jun 20;24(12):
pubmed: 31226738
Public Health Nutr. 2010 Sep;13(9):1403-9
pubmed: 20059796
Angew Chem Int Ed Engl. 2005 Jun 20;44(25):3814-39
pubmed: 15900534
Mol Cell Proteomics. 2013 Dec;12(12):3759-77
pubmed: 24030100
Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1488-93
pubmed: 17242355
Cell Rep. 2018 Mar 6;22(10):2784-2796
pubmed: 29514104
J Biol Chem. 2013 Aug 9;288(32):23331-47
pubmed: 23798682
FEBS J. 2021 Dec;288(24):6913-6926
pubmed: 33301645
Biochemistry. 2014 Jan 21;53(2):397-412
pubmed: 24359314
Bioorg Med Chem Lett. 2016 Jan 1;26(1):87-93
pubmed: 26602279
Mol Oncol. 2016 Jun;10(6):910-20
pubmed: 27067626
J Comput Chem. 2010 Jan 30;31(2):455-61
pubmed: 19499576
Mol Cell Proteomics. 2005 Dec;4(12):2010-21
pubmed: 16249172
Neurochem Res. 2014 Jun;39(6):1171-81
pubmed: 24728903
Int J Mol Sci. 2020 Jan 13;21(2):
pubmed: 31941000
Nat Rev Mol Cell Biol. 2001 Oct;2(10):749-59
pubmed: 11584302
Am J Clin Nutr. 2020 Aug 1;112(2):343-353
pubmed: 32320019
J Neurosci Res. 2008 Feb 15;86(3):668-74
pubmed: 17893926
EMBO J. 2000 Jun 15;19(12):2775-85
pubmed: 10856223
Biochim Biophys Acta. 2013 Oct;1832(10):1673-96
pubmed: 23707412
Bioinformatics. 2010 Apr 1;26(7):966-8
pubmed: 20147306
Mol Cell Proteomics. 2019 Oct;18(10):2058-2077
pubmed: 31427368
Biochem Pharmacol. 2022 Jan;195:114868
pubmed: 34863978
J Biol Chem. 2000 Feb 11;275(6):4066-71
pubmed: 10660565
Proteomics. 2013 Jan;13(1):22-4
pubmed: 23148064
J Clin Med. 2020 Jan 09;9(1):
pubmed: 31936517
Sci Rep. 2015 Oct 29;5:15709
pubmed: 26511732
Ann N Y Acad Sci. 2019 Sep;1451(1):112-129
pubmed: 30648269
EMBO J. 1993 Feb;12(2):803-8
pubmed: 8382613
Proteomes. 2015 Aug 07;3(3):160-183
pubmed: 28248267
Proteins. 2010 Jul;78(9):2029-40
pubmed: 20455260
J Cell Sci. 2014 Jun 1;127(Pt 11):2391-400
pubmed: 24879856
Neuropsychopharmacology. 2021 Nov;46(12):2132-2139
pubmed: 34302059
Anal Chem. 2003 Feb 1;75(3):663-70
pubmed: 12585499
N Biotechnol. 2016 Sep 25;33(5 Pt A):524-36
pubmed: 26316256
Lancet Neurol. 2017 Nov;16(11):898-907
pubmed: 29029846
J Med Chem. 2004 Mar 25;47(7):1750-9
pubmed: 15027866
EMBO J. 2020 Jun 2;39(11):e104150
pubmed: 32347567
J Struct Funct Genomics. 2007 Sep;8(2-3):121-40
pubmed: 18058037