Increased Phospho-AKT in Blood Cells from LRRK2 G2019S Mutation Carriers.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
revised:
15
07
2022
received:
28
03
2022
accepted:
29
07
2022
pubmed:
6
8
2022
medline:
26
10
2022
entrez:
5
8
2022
Statut:
ppublish
Résumé
The purpose of this study was to investigate whether differential phosphorylation states of blood markers can identify patients with LRRK2 Parkinson's disease (PD). We assessed phospho(P)-Ser-935-LRRK2 and P-Ser-473-AKT levels in peripheral blood cells from patients with G2019S LRRK2-associated PD (L2PD, n = 31), G2019S LRRK2 non-manifesting carriers (L2NMC, n = 26), idiopathic PD (iPD, n = 25), and controls (n = 40, total n = 122). We found no differences at P-Ser-935-LRRK2 between groups but detected a specific increase of P-Ser-473-AKT levels in all G2019S carriers, either L2PD or L2NMC, absent in iPD. Although insensitive to LRRK2 inhibition, our study identifies P-Ser-473-AKT as an endogenous candidate biomarker for peripheral inflammation in G2019S carriers using accessible blood cells. ANN NEUROL 2022;92:888-894.
Identifiants
pubmed: 35929078
doi: 10.1002/ana.26469
pmc: PMC9827833
doi:
Substances chimiques
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Biomarkers
0
LRRK2 protein, human
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
888-894Informations de copyright
© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
J Neuroinflammation. 2022 May 22;19(1):113
pubmed: 35599331
J Immunol. 2004 Jun 15;172(12):7583-91
pubmed: 15187138
J Neurosci. 2008 Dec 31;28(53):14363-71
pubmed: 19118169
J Transl Med. 2019 Jan 22;17(1):37
pubmed: 30670047
Nat Rev Neurol. 2020 Feb;16(2):97-107
pubmed: 31980808
J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181-4
pubmed: 1564476
Brain Res Dev Brain Res. 1999 Nov 18;117(2):145-52
pubmed: 10567732
Exp Neurobiol. 2019 Apr;28(2):134-145
pubmed: 31138985
Cell. 2017 Apr 20;169(3):381-405
pubmed: 28431241
Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16842-7
pubmed: 16269541
J Neurol Sci. 2019 Jul 15;402:121-130
pubmed: 31129265
J Leukoc Biol. 2010 May;87(5):895-904
pubmed: 20103769
Mov Disord. 2006 Nov;21(11):1954-9
pubmed: 16991141
Biochem Soc Trans. 2019 Dec 20;47(6):1581-1595
pubmed: 31769472
Mol Neurobiol. 2018 Oct;55(10):7728-7742
pubmed: 29460266
Mov Disord. 2022 May;37(5):1004-1015
pubmed: 35049090
Nat Genet. 2010 Sep;42(9):781-5
pubmed: 20711177
Sci Rep. 2019 Mar 14;9(1):4515
pubmed: 30872638
Cell Death Differ. 2010 Feb;17(2):324-35
pubmed: 19745829
Biochem J. 2018 Jan 2;475(1):23-44
pubmed: 29127255
Biochim Biophys Acta Mol Cell Res. 2020 Nov 12;1868(2):118907
pubmed: 33189783
J Parkinsons Dis. 2020;10(2):623-629
pubmed: 32007961
EMBO J. 2020 Oct 15;39(20):e104862
pubmed: 32853409
Neurosci Lett. 2009 Dec 18;467(1):30-5
pubmed: 19800394
Hum Mol Genet. 2016 May 15;25(10):1965-1978
pubmed: 26931464
J Neurol Neurosurg Psychiatry. 2007 Jun;78(6):626-8
pubmed: 17210620
Circ Res. 2012 Oct 26;111(10):1297-307
pubmed: 22927331
Biochem J. 2010 Sep 15;430(3):405-13
pubmed: 20659021
Nat Rev Immunol. 2022 Nov;22(11):657-673
pubmed: 35246670
Cell Cycle. 2009 Sep 1;8(17):2789-93
pubmed: 19652548
J Med Chem. 2017 Apr 13;60(7):2983-2992
pubmed: 28245354
Cell Stress Chaperones. 2021 Nov;26(6):871-887
pubmed: 34386944
Curr Neuropharmacol. 2016;14(3):214-25
pubmed: 26517051
Mov Disord. 2016 Jun;31(6):889-97
pubmed: 26917005
Neurotox Res. 2019 Apr;35(3):775-795
pubmed: 30707354
J Parkinsons Dis. 2022;12(s1):S29-S43
pubmed: 35661019
Neurology. 2014 Aug 5;83(6):568-9
pubmed: 25008396
Hum Mol Genet. 2015 Sep 1;24(17):4879-900
pubmed: 26056228
Front Neurosci. 2020 Jun 16;14:527
pubmed: 32612495
Cell Physiol Biochem. 2013;31(6):795-804
pubmed: 23735868
J Neuroinflammation. 2016 May 24;13(1):122
pubmed: 27220776
Hum Mol Genet. 2013 Mar 1;22(5):1039-49
pubmed: 23223016
Acta Neuropathol. 2021 Sep;142(3):475-494
pubmed: 34125248
Mov Disord. 2020 Nov;35(11):2095-2100
pubmed: 32652692
Hum Mol Genet. 2014 Nov 1;23(21):5649-58
pubmed: 24916379