Huntingtin Co-Isolates with Small Extracellular Vesicles from Blood Plasma of TgHD and KI-HD Pig Models of Huntington's Disease and Human Blood Plasma.
Huntington´s disease
KI-HD
TgHD
biomarker
exosome
extracellular vesicle
fragment
huntingtin
neurodegenerative disease
pig model
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
17 May 2022
17 May 2022
Historique:
received:
19
04
2022
revised:
12
05
2022
accepted:
15
05
2022
entrez:
28
5
2022
pubmed:
29
5
2022
medline:
1
6
2022
Statut:
epublish
Résumé
(1) Background: Huntington's disease (HD) is rare incurable hereditary neurodegenerative disorder caused by CAG repeat expansion in the gene coding for the protein huntingtin (HTT). Mutated huntingtin (mHTT) undergoes fragmentation and accumulation, affecting cellular functions and leading to neuronal cell death. Porcine models of HD are used in preclinical testing of currently emerging disease modifying therapies. Such therapies are aimed at reducing mHTT expression, postpone the disease onset, slow down the progression, and point out the need of biomarkers to monitor disease development and therapy efficacy. Recently, extracellular vesicles (EVs), particularly exosomes, gained attention as possible carriers of disease biomarkers. We aimed to characterize HTT and mHTT forms/fragments in blood plasma derived EVs in transgenic (TgHD) and knock-in (KI-HD) porcine models, as well as in HD patients' plasma. (2) Methods: Small EVs were isolated by ultracentrifugation and HTT forms were visualized by western blotting. (3) Results: The full length 360 kDa HTT co-isolated with EVs from both the pig model and HD patient plasma. In addition, a ~70 kDa mutant HTT fragment was specific for TgHD pigs. Elevated total huntingtin levels in EVs from plasma of HD groups compared to controls were observed in both pig models and HD patients, however only in TgHD were they significant (
Identifiants
pubmed: 35628406
pii: ijms23105598
doi: 10.3390/ijms23105598
pmc: PMC9147436
pii:
doi:
Substances chimiques
Biomarkers
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Czech Science Foundation
ID : 19-01747S
Organisme : Cooperatio Program, research area Neuroscience
ID : Cooperatio
Organisme : General University Hospital in Prague
ID : MZ-ČR RVO- VFN 00064165
Organisme : General University Hospital in Prague
ID : GIP 22-SL-05-212
Organisme : Institute of Animal Physiology and Genetics
ID : RVO:67985904
Organisme : Czech health research council
ID : MZ NU20-04-00136
Organisme : European Reference Network for Rare Neurological Diseases
ID : 739510
Références
Cell Mol Life Sci. 2018 Aug;75(15):2873-2886
pubmed: 29441425
J Extracell Vesicles. 2015 Jul 17;4:27031
pubmed: 26194179
Neurodegener Dis. 2016;16(3-4):245-59
pubmed: 26959244
Dis Model Mech. 2019 Dec 12;13(2):
pubmed: 31704691
FASEB Bioadv. 2021 Jul 23;3(9):665-675
pubmed: 34485835
Nat Rev Neurol. 2020 Oct;16(10):529-546
pubmed: 32796930
Fac Rev. 2021 Oct 21;10:77
pubmed: 34746930
Genes (Basel). 2019 Nov 09;10(11):
pubmed: 31717496
Expert Rev Neurother. 2019 Oct;19(10):983-995
pubmed: 31181964
Dis Model Mech. 2018 Oct 24;11(10):
pubmed: 30254085
Melanoma Res. 2003 Dec;13(6):543-8
pubmed: 14646615
Proteomes. 2019 Apr 25;7(2):
pubmed: 31027284
Brain. 2021 Feb 12;144(1):288-309
pubmed: 33246331
Neural Plast. 2021 May 16;2021:8884642
pubmed: 34054944
Front Physiol. 2012 Jul 05;3:229
pubmed: 22783199
Int J Mol Sci. 2019 Apr 08;20(7):
pubmed: 30965555
J Neurol. 2018 Nov;265(11):2704-2712
pubmed: 30209650
Acta Neuropathol. 2016 Oct;132(4):577-92
pubmed: 27221146
Prog Mol Biol Transl Sci. 2012;107:189-214
pubmed: 22482451
Anal Biochem. 2009 Dec 1;395(1):8-15
pubmed: 19664996
Dialogues Clin Neurosci. 2016 Mar;18(1):91-8
pubmed: 27069383
Physiol Res. 2016;65(1):155-63
pubmed: 26596319
Methods. 2012 Feb;56(2):293-304
pubmed: 22285593
Front Physiol. 2018 Oct 23;9:1479
pubmed: 30405435
Eur J Neurol. 2018 Jan;25(1):24-34
pubmed: 28817209
Cell Mol Neurobiol. 2016 Apr;36(3):459-70
pubmed: 26951563
Clin Interv Aging. 2021 Feb 10;16:257-274
pubmed: 33603351
Front Neurosci. 2017 Mar 31;11:149
pubmed: 28611571
Neurosci Res. 2020 Nov;160:43-49
pubmed: 31669371
Dev Biol. 2014 Jul 15;391(2):230-40
pubmed: 24780625
Traffic. 2001 Jun;2(6):385-94
pubmed: 11389766
J Extracell Vesicles. 2015 Mar 31;4:25530
pubmed: 25833224
Neurobiol Dis. 2019 Oct;130:104512
pubmed: 31229685
Neurosci Lett. 2017 Mar 22;644:94-99
pubmed: 28223160
Nat Biotechnol. 2011 Apr;29(4):341-5
pubmed: 21423189
Int J Mol Sci. 2021 Jun 18;22(12):
pubmed: 34207177
eNeuro. 2018 Oct 10;5(4):
pubmed: 30310861
Dis Model Mech. 2020 Oct 26;13(10):
pubmed: 33106318
Curr Protoc Cell Biol. 2006 Apr;Chapter 3:Unit 3.22
pubmed: 18228490
Neurology. 2015 Jul 7;85(1):40-7
pubmed: 26062630
Mol Ther. 2018 Sep 5;26(9):2163-2177
pubmed: 30007561
Cell Biosci. 2021 Dec 21;11(1):218
pubmed: 34933675
J Neurosci. 2017 Sep 27;37(39):9550-9563
pubmed: 28893927
Methods Mol Biol. 2018;1780:179-207
pubmed: 29856020
J Card Surg. 2022 Apr;37(4):909-918
pubmed: 35106827
J Huntingtons Dis. 2020;9(3):201-216
pubmed: 32925082
Neuron. 2016 Mar 2;89(5):910-26
pubmed: 26938440
Neurol Clin. 2015 Feb;33(1):101-14
pubmed: 25432725
Lancet Neurol. 2009 Aug;8(8):765-74
pubmed: 19608102
J Neurol Neurosurg Psychiatry. 2019 Mar;90(3):272-283
pubmed: 30567722
Nucleosides Nucleotides Nucleic Acids. 2022;41(3):231-238
pubmed: 32933349
Cells. 2022 Jan 27;11(3):
pubmed: 35159246
Int J Mol Sci. 2021 Oct 05;22(19):
pubmed: 34639106
FASEB J. 2021 Oct;35(10):e21895
pubmed: 34478572
Nat Rev Mol Cell Biol. 2018 Apr;19(4):213-228
pubmed: 29339798
J Huntingtons Dis. 2013;2(1):47-68
pubmed: 25063429
Int J Mol Sci. 2021 Apr 15;22(8):
pubmed: 33920936
Lancet Neurol. 2011 Jan;10(1):83-98
pubmed: 21163446
Toxicol Pathol. 2016 Apr;44(3):299-314
pubmed: 26839324
Mol Cell Neurosci. 2006 Apr;31(4):642-8
pubmed: 16446100
Sci Transl Med. 2021 Apr 7;13(588):
pubmed: 33827977
J Clin Invest. 2015 May;125(5):1979-86
pubmed: 25844897
J Biol Chem. 2014 Mar 7;289(10):6709-6726
pubmed: 24407293
Int J Mol Sci. 2016 Feb 06;17(2):170
pubmed: 26861301
Ann Clin Transl Neurol. 2015 Apr;2(4):353-61
pubmed: 25909081
Metab Brain Dis. 2022 Aug;37(6):1757-1771
pubmed: 34704220
Clin Chim Acta. 2016 Nov 1;462:118-126
pubmed: 27609124
Biomol Concepts. 2016 Feb;7(1):53-68
pubmed: 26812803
JAMA Neurol. 2019 Nov 01;76(11):1340-1351
pubmed: 31305918
Neurodegener Dis. 2018;18(2-3):107-119
pubmed: 29870995
Sci Rep. 2020 Jan 23;10(1):1039
pubmed: 31974468
Cell Mol Life Sci. 2021 Jan;78(2):561-572
pubmed: 32803397
PLoS One. 2015 Dec 21;10(12):e0145686
pubmed: 26690353
Int J Mol Sci. 2020 Nov 05;21(21):
pubmed: 33167595
Proc Natl Acad Sci U S A. 2014 Mar 4;111(9):3620-5
pubmed: 24550511
PLoS One. 2020 Aug 19;15(8):e0236439
pubmed: 32813744
J Extracell Vesicles. 2015 May 14;4:27066
pubmed: 25979354
Cells. 2020 Nov 15;9(11):
pubmed: 33203181
Front Cell Neurosci. 2021 Jan 28;14:612560
pubmed: 33584205
J Neurosci. 2014 Nov 12;34(46):15482-9
pubmed: 25392515
Eur Biophys J. 2008 Mar;37(3):323-32
pubmed: 18064447
Dis Model Mech. 2019 Dec 12;13(2):
pubmed: 31645369
Pharmaceutics. 2022 Mar 18;14(3):
pubmed: 35336049
J Extracell Vesicles. 2018 Nov 23;7(1):1535750
pubmed: 30637094
J Neurotrauma. 2012 Feb 10;29(3):499-513
pubmed: 22029501
Front Neurosci. 2017 Feb 27;11:82
pubmed: 28289371
Nat Neurosci. 2018 Oct;21(10):1332-1340
pubmed: 30250260
Methods Mol Biol. 2018;1740:69-83
pubmed: 29388137
Acta Neuropathol. 2014 Nov;128(5):639-650
pubmed: 24997849
Alzheimers Dement. 2015 Jun;11(6):600-7.e1
pubmed: 25130657
J Extracell Vesicles. 2020 Jan 5;9(1):1699367
pubmed: 32002166
FASEB Bioadv. 2021 May 13;3(8):577-592
pubmed: 34377954
Annu Rev Cell Dev Biol. 2014;30:255-89
pubmed: 25288114
Ageing Res Rev. 2021 Aug;69:101358
pubmed: 33979693
CNS Neurol Disord Drug Targets. 2021;20(10):894-903
pubmed: 33845728
Alzheimers Dement (Amst). 2016 May 07;3:63-72
pubmed: 27408937
J Biol Chem. 2019 Mar 8;294(10):3744-3759
pubmed: 30635404
J Extracell Vesicles. 2014 Sep 18;3:
pubmed: 25317274
Front Aging Neurosci. 2021 Dec 16;13:790863
pubmed: 34975460
Int J Mol Sci. 2016 Feb 06;17(2):173
pubmed: 26861304
Sci Rep. 2017 Apr 19;7(1):956
pubmed: 28424476
Lancet Neurol. 2017 Oct;16(10):837-847
pubmed: 28920889
Swiss Med Wkly. 2015 Nov 12;145:w14204
pubmed: 26561744
PLoS One. 2014 May 09;9(5):e96854
pubmed: 24816435