A Secretory Vesicle Failure in Parkinson's Disease Occurs in Human Platelets.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
15
02
2022
received:
03
11
2021
accepted:
18
02
2022
pubmed:
1
3
2022
medline:
20
4
2022
entrez:
28
2
2022
Statut:
ppublish
Résumé
The presence of elevated dopamine (DA) and its major metabolites in the cytosol of neurons has been associated with their vulnerability in Parkinson's disease (PD). Over 99% of the cell's amines are confined to secretory vesicles (SVs), making these structures fundamental in the regulation of cytosolic DA levels. SVs of platelets use similar, if not the same mechanisms to accumulate serotonin in SVs as dopaminergic neurons do to store DA. Hence, any functional defects in platelets probably mirrors events in DA neurons. We have isolated fresh platelets from the blood of 75 PD patients, 116 matched controls and 24 patients with Parkinsonism, assaying serotonin handling (basal content, accumulation, secretion and spontaneous leakage). We found a dramatic decrease in the serotonin content and uptake by SVs, as well as decreased thrombin-induced release by platelets from PD patients but not in those from most Parkinsonism cases. Platelets from PD patients also failed to retain serotonin in SVs. These findings indicate a functional impairment in the handling of amines by SVs in PD patients. This defect may serve as a biomarker of PD, and the approach described here may be potentially used for the subclinical detection of PD and to establish a platform to assay disease modifying drugs. ANN NEUROL 2022.
Identifiants
pubmed: 35226382
doi: 10.1002/ana.26335
pmc: PMC9315021
doi:
Substances chimiques
Serotonin
333DO1RDJY
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
697-703Informations de copyright
© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Pharmacol Ther. 2014 Dec;144(3):268-82
pubmed: 24945828
Biochem Med. 1972 Jun;6(3):210-5
pubmed: 5041890
Mov Disord. 2002 Jul;17(4):775-81
pubmed: 12210875
Nat Rev Neurosci. 2010 Dec;11(12):791-7
pubmed: 21088684
Pharmacol Rev. 2004 Sep;56(3):331-49
pubmed: 15317907
J Neurol Neurosurg Psychiatry. 1978 Jul;41(7):589-92
pubmed: 690635
Neurochem Res. 1997 Aug;22(8):921-32
pubmed: 9239747
J Neurosci. 2008 Mar 26;28(13):3350-8
pubmed: 18367602
J Neurosci. 2003 Jul 2;23(13):5835-45
pubmed: 12843288
Ann Neurol. 2011 Mar;69(3):570-80
pubmed: 21400565
Br J Pharmacol. 1970 Aug;39(4):779-88
pubmed: 5485151
Neurology. 1975 Jan;25(1):1-9
pubmed: 234181
J Biol Chem. 2008 Aug 15;283(33):22383-9
pubmed: 18562320
Nat Rev Dis Primers. 2017 Mar 23;3:17013
pubmed: 28332488
Mov Disord. 1993;8(1):83-6
pubmed: 8093549
Biophys J. 2011 Nov 16;101(10):2351-9
pubmed: 22098733
Parkinsonism Relat Disord. 2015 Aug;21(8):882-7
pubmed: 26028271
Life Sci. 1993;53(23):1753-9
pubmed: 8246671
Nature. 1997 Oct 2;389(6650):509-12
pubmed: 9333242
Sci Rep. 2013;3:1447
pubmed: 23486177
Cell Commun Signal. 2013 May 17;11(1):34
pubmed: 23683503
Nature. 1976 Aug 12;262(5569):596-8
pubmed: 958421
J Neurochem. 2013 Sep;126(5):591-603
pubmed: 23786406
BMJ. 2007 Sep 1;335(7617):441-5
pubmed: 17762036
Mov Disord. 2011 Oct;26(12):2160-8
pubmed: 21887711
Nat Med. 2020 Feb;26(2):289-299
pubmed: 31988461
Front Biosci (Landmark Ed). 2012 Jun 01;17(7):2740-67
pubmed: 22652810
J Neurosci. 2014 Jun 11;34(24):8210-8
pubmed: 24920625
Neuron. 2009 Apr 30;62(2):218-29
pubmed: 19409267