mGluR5 PAMs rescue cortical and behavioural defects in a mouse model of CDKL5 deficiency disorder.
Journal
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
ISSN: 1740-634X
Titre abrégé: Neuropsychopharmacology
Pays: England
ID NLM: 8904907
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
04
02
2022
accepted:
19
07
2022
revised:
04
07
2022
medline:
5
5
2023
pubmed:
10
8
2022
entrez:
9
8
2022
Statut:
ppublish
Résumé
Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a devastating rare neurodevelopmental disease without a cure, caused by mutations of the serine/threonine kinase CDKL5 highly expressed in the forebrain. CDD is characterized by early-onset seizures, severe intellectual disabilities, autistic-like traits, sensorimotor and cortical visual impairments (CVI). The lack of an effective therapeutic strategy for CDD urgently demands the identification of novel druggable targets potentially relevant for CDD pathophysiology. To this aim, we studied Class I metabotropic glutamate receptors 5 (mGluR5) because of their important role in the neuropathological signs produced by the lack of CDKL5 in-vivo, such as defective synaptogenesis, dendritic spines formation/maturation, synaptic transmission and plasticity. Importantly, mGluR5 function strictly depends on the correct expression of the postsynaptic protein Homer1bc that we previously found atypical in the cerebral cortex of Cdkl5
Identifiants
pubmed: 35945276
doi: 10.1038/s41386-022-01412-3
pii: 10.1038/s41386-022-01412-3
pmc: PMC10156697
mid: EMS151224
doi:
Substances chimiques
CDKL5 protein, mouse
EC 2.7.11.22
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
877-886Informations de copyright
© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.
Références
Mol Pharmacol. 2008 Mar;73(3):909-18
pubmed: 18056795
Hum Mol Genet. 2017 Sep 15;26(18):3520-3530
pubmed: 28641386
J Neurosci. 2000 Dec 1;20(23):8710-6
pubmed: 11102477
Proc Natl Acad Sci U S A. 2013 May 28;110(22):9118-23
pubmed: 23671101
Eur J Neurosci. 1996 Jul;8(7):1488-500
pubmed: 8758956
Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):E305-12
pubmed: 23269840
J Neurosci. 2016 Aug 24;36(34):8802-14
pubmed: 27559164
J Neurosci. 2019 Jun 12;39(24):4814-4828
pubmed: 30952813
Nat Cell Biol. 2012 Sep;14(9):911-23
pubmed: 22922712
Nature. 2011 Nov 23;480(7375):63-8
pubmed: 22113615
Nat Neurosci. 2012 Jan 22;15(3):431-40, S1
pubmed: 22267161
Front Cell Neurosci. 2016 Nov 28;10:261
pubmed: 27965538
Nat Protoc. 2009;4(10):1560-4
pubmed: 19798088
Neuron. 2018 Jun 27;98(6):1080-1098
pubmed: 29953871
Biochem Biophys Res Commun. 2008 Dec 26;377(4):1162-7
pubmed: 18977197
J Physiol. 2020 Jun;598(11):2183-2197
pubmed: 32246769
Mol Cell Neurosci. 2018 Sep;91:82-94
pubmed: 29777761
J Biol Chem. 2008 Oct 31;283(44):30101-11
pubmed: 18701457
EMBO J. 2018 Dec 14;37(24):
pubmed: 30266824
J Neurosci. 2005 Sep 28;25(39):8908-16
pubmed: 16192381
J Biol Chem. 2011 Oct 7;286(40):34839-50
pubmed: 21795692
J Pharmacol Exp Ther. 2011 Sep;338(3):897-905
pubmed: 21636656
Biol Psychiatry. 2016 Aug 15;80(4):302-311
pubmed: 26452614
Hum Mol Genet. 2005 Jul 15;14(14):1935-46
pubmed: 15917271
Hum Mol Genet. 2018 May 1;27(9):1572-1592
pubmed: 29474534
eNeuro. 2018 Sep 24;5(5):
pubmed: 30255129
Neurobiol Dis. 2014 Oct;70:53-68
pubmed: 24952363
Hum Mol Genet. 2016 May 15;25(10):1990-2004
pubmed: 26936821
Nat Rev Neurosci. 2001 Dec;2(12):880-8
pubmed: 11733795
Mol Psychiatry. 2017 May;22(5):689-702
pubmed: 27021819
Neurobiol Dis. 2017 Oct;106:158-170
pubmed: 28688852
Epilepsia. 2019 Aug;60(8):1733-1742
pubmed: 31313283
Nat Commun. 2019 Mar 29;10(1):1431
pubmed: 30926797
Hum Mol Genet. 2018 Jun 15;27(12):2052-2063
pubmed: 29618004
Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):6055-60
pubmed: 17389377
Mol Psychiatry. 2021 Nov;26(11):7047-7068
pubmed: 33888873
Nat Commun. 2017 Oct 24;8(1):1103
pubmed: 29062097
Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21516-21
pubmed: 23236174
Front Pharmacol. 2012 Nov 27;3:199
pubmed: 23205012
Cell Tissue Res. 2006 Nov;326(2):483-504
pubmed: 16847639
PLoS One. 2010 Mar 18;5(3):e9755
pubmed: 20305784
Neurosci Lett. 2012 Aug 22;524(1):65-8
pubmed: 22819970
PLoS One. 2016 Feb 05;11(2):e0148634
pubmed: 26849555
PLoS One. 2014 May 16;9(5):e91613
pubmed: 24838000
PLoS One. 2012;7(1):e28666
pubmed: 22238580
Front Pharmacol. 2012 Nov 01;3:189
pubmed: 23125836
Exp Neurol. 2019 Jan;311:194-204
pubmed: 30316834
J Neurosci. 2006 Mar 1;26(9):2544-54
pubmed: 16510732
Neuroscience. 2020 Oct 1;445:130-143
pubmed: 31472213
Genome Biol. 2007;8(2):206
pubmed: 17316461
Hum Mol Genet. 2017 Jun 15;26(12):2290-2298
pubmed: 28369421
Neuropsychopharmacology. 2018 May;43(6):1457-1465
pubmed: 29206810
Neuron. 1999 Jul;23(3):583-92
pubmed: 10433269
Epilepsia. 2021 Feb;62(2):517-528
pubmed: 33400301
J Neurosci. 2003 Jul 16;23(15):6327-37
pubmed: 12867517
Hum Mol Genet. 2019 Sep 1;28(17):2851-2861
pubmed: 31108505
J Clin Invest. 2021 Oct 15;131(20):
pubmed: 34651584
Nat Protoc. 2007;2(10):2345-7
pubmed: 17947976
EMBO J. 2018 Dec 14;37(24):
pubmed: 30266825
Biomolecules. 2020 Mar 18;10(3):
pubmed: 32197322