Alpha-Synuclein in the Regulation of Brain Endothelial and Perivascular Cells: Gaps and Future Perspectives.
Animals
Biomarkers
Blood-Brain Barrier
/ metabolism
Brain
/ metabolism
Cell Communication
Central Nervous System
/ metabolism
Disease Susceptibility
Endothelial Cells
/ metabolism
Gene Expression Regulation
Humans
Microglia
/ immunology
Neurodegenerative Diseases
/ etiology
alpha-Synuclein
/ genetics
Parkinson's disease
blood brain barrier
border-associated macrophages
endothelial cells
perivascular cells
α-synuclein
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
29
09
2020
accepted:
27
01
2021
entrez:
8
3
2021
pubmed:
9
3
2021
medline:
1
7
2021
Statut:
epublish
Résumé
Misfolded proteins, inflammation, and vascular alterations are common pathological hallmarks of neurodegenerative diseases. Alpha-synuclein is a small synaptic protein that was identified as a major component of Lewy bodies and Lewy neurites in the brain of patients affected by Parkinson's disease (PD), Lewy body dementia (LBD), and other synucleinopathies. It is mainly involved in the regulation of synaptic vesicle trafficking but can also control mitochondrial/endoplasmic reticulum (ER) homeostasis, lysosome/phagosome function, and cytoskeleton organization. Recent evidence supports that the pathological forms of α-synuclein can also reduce the release of vasoactive and inflammatory mediators from endothelial cells (ECs) and modulates the expression of tight junction (TJ) proteins important for maintaining the blood-brain barrier (BBB). This hints that α-synuclein deposition can affect BBB integrity. Border associated macrophages (BAMs) are brain resident macrophages found in association with the vasculature (PVMs), meninges (MAMs), and choroid plexus (CPMs). Recent findings indicate that these cells play distinct roles in stroke and neurodegenerative disorders. Although many studies have addressed how α-synuclein may modulate microglia, its effect on BAMs has been scarcely investigated. This review aims at summarizing the main findings supporting how α-synuclein can affect ECs and/or BAMs function as well as their interplay and effect on other cells in the brain perivascular environment in physiological and pathological conditions. Gaps of knowledge and new perspectives on how this protein can contribute to neurodegeneration by inducing BBB homeostatic changes in different neurological conditions are highlighted.
Identifiants
pubmed: 33679750
doi: 10.3389/fimmu.2021.611761
pmc: PMC7933041
doi:
Substances chimiques
Biomarkers
0
alpha-Synuclein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
611761Informations de copyright
Copyright © 2021 Bogale, Faustini, Longhena, Mitola, Pizzi and Bellucci.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Nat Immunol. 2016 Jul;17(7):797-805
pubmed: 27135602
Nat Cell Biol. 2002 Feb;4(2):160-4
pubmed: 11813001
Aging Dis. 2020 Mar 9;11(2):254-268
pubmed: 32257540
J Neuroinflammation. 2010 Dec 06;7:89
pubmed: 21134289
J Immunol Res. 2017;2017:5150678
pubmed: 29410971
Hum Mol Genet. 2020 Nov 4;29(18):3107-3121
pubmed: 32954426
Apoptosis. 2001 Feb-Apr;6(1-2):69-81
pubmed: 11321043
Glia. 2021 Mar;69(3):681-696
pubmed: 33045109
Neurobiol Dis. 2016 Sep;93:215-25
pubmed: 27234656
Int J Mol Sci. 2019 Jan 02;20(1):
pubmed: 30609739
Parkinsonism Relat Disord. 2010 Jan;16(1):57-9
pubmed: 19487152
Heliyon. 2019 Oct 18;5(10):e02590
pubmed: 31692680
J Parkinsons Dis. 2015;5(4):821-36
pubmed: 26444086
J Neurochem. 2016 Oct;139 Suppl 1:240-255
pubmed: 26190401
Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):E1926-35
pubmed: 25825709
Front Cell Neurosci. 2013 Apr 23;7:44
pubmed: 23630462
J Neurosci. 2016 May 4;36(18):5144-59
pubmed: 27147665
Sci Rep. 2020 Jan 14;10(1):204
pubmed: 31937832
Nat Rev Neurosci. 2016 Mar;17(3):160-72
pubmed: 26891626
Circ Res. 2007 Feb 2;100(2):158-73
pubmed: 17272818
Exp Neurol. 2016 Nov;285(Pt A):72-81
pubmed: 27632900
Biochem Biophys Res Commun. 2009 Mar 27;381(1):39-43
pubmed: 19351591
J Neuroinflammation. 2019 Dec 12;16(1):263
pubmed: 31831012
Front Neurol. 2017 Oct 04;8:527
pubmed: 29046661
Neurosci Lett. 2002 Jun 21;326(1):5-8
pubmed: 12052525
Sci Rep. 2019 Jul 29;9(1):10919
pubmed: 31358782
Pathol Int. 2002 Sep;52(9):572-7
pubmed: 12406186
Adv Exp Med Biol. 2019;1175:335-353
pubmed: 31583594
Sci Rep. 2017 Feb 23;7:42984
pubmed: 28230073
Front Neurosci. 2019 Dec 04;13:1291
pubmed: 31866808
Exp Ther Med. 2020 Aug;20(2):1021-1029
pubmed: 32742344
Mol Biol Cell. 2010 Jun 1;21(11):1850-63
pubmed: 20392839
Acta Neuropathol Commun. 2017 Sep 13;5(1):71
pubmed: 28903781
Mov Disord. 2016 Feb;31(2):169-77
pubmed: 26790375
Brain Pathol. 2019 Mar;29(2):176-192
pubmed: 30192999
J Neural Transm Suppl. 2000;(58):143-51
pubmed: 11128604
J Mol Biol. 2009 Jun 5;389(2):413-24
pubmed: 19285989
Neurosci Lett. 1994 Jan 3;165(1-2):208-10
pubmed: 8015728
Biochem Biophys Res Commun. 1997 Aug 28;237(3):611-6
pubmed: 9299413
Trends Cardiovasc Med. 2005 Nov;15(8):302-8
pubmed: 16297768
J Neuroinflammation. 2019 Dec 30;16(1):283
pubmed: 31888724
Sci Signal. 2017 Jul 11;10(487):
pubmed: 28698213
Hum Mol Genet. 2006 Oct 15;15(20):3012-23
pubmed: 16959795
Inflammopharmacology. 2018 Apr;26(2):349-360
pubmed: 29027056
CNS Neurosci Ther. 2019 Dec;25(12):1318-1328
pubmed: 31749316
Nat Commun. 2020 Mar 13;11(1):1386
pubmed: 32170061
Neurosci Lett. 2013 Aug 26;548:190-5
pubmed: 23792198
Cell Tissue Res. 2018 Jul;373(1):137-148
pubmed: 29119326
Front Aging Neurosci. 2017 Oct 10;9:330
pubmed: 29066967
Sci Rep. 2020 Apr 21;10(1):6682
pubmed: 32317654
Nat Rev Immunol. 2018 Nov;18(11):689-702
pubmed: 30127389
J Biol Chem. 2005 Mar 11;280(10):9595-603
pubmed: 15615727
Proc Natl Acad Sci U S A. 1998 May 26;95(11):6469-73
pubmed: 9600990
Glia. 2005 Feb;49(3):375-84
pubmed: 15538754
Neurobiol Dis. 2018 Nov;119:121-135
pubmed: 30092270
Thromb Haemost. 2010 Jan;103(1):40-55
pubmed: 20062930
J Am Chem Soc. 2013 Mar 13;135(10):3865-72
pubmed: 23398399
J Cereb Blood Flow Metab. 2011 Mar;31(3):913-23
pubmed: 20877387
Eur J Neurosci. 2001 Nov;14(10):1651-8
pubmed: 11860459
Ann Clin Transl Neurol. 2019 Mar 12;6(4):788-794
pubmed: 31020003
Virus Res. 2015 Sep 2;207:38-46
pubmed: 25456401
Neurobiol Aging. 2003 Mar-Apr;24(2):197-211
pubmed: 12498954
J Neurosci. 2016 Jun 29;36(26):7055-65
pubmed: 27358461
Front Aging Neurosci. 2020 Mar 24;12:68
pubmed: 32265684
Mol Cells. 2000 Feb 29;10(1):65-70
pubmed: 10774749
Eur J Neurosci. 2005 Sep;22(5):1158-68
pubmed: 16176358
J Parkinsons Dis. 2017;7(s1):S51-S69
pubmed: 28282814
Nat Rev Dis Primers. 2017 Mar 23;3:17013
pubmed: 28332488
Front Neuroanat. 2015 Feb 23;9:17
pubmed: 25755636
Semin Immunopathol. 2009 Nov;31(4):497-511
pubmed: 19779720
FEBS Lett. 2000 May 26;474(1):116-9
pubmed: 10828462
Neurosci Lett. 2000 Jun 16;287(1):65-7
pubmed: 10841992
Neurol Sci. 2016 May;37(5):749-54
pubmed: 26829934
Cold Spring Harb Perspect Med. 2012 Jan;2(1):a006429
pubmed: 22315715
Nat Rev Immunol. 2007 Oct;7(10):803-15
pubmed: 17893694
Cold Spring Harb Perspect Biol. 2015 Jan 05;7(1):a020412
pubmed: 25561720
Brain Res. 2011 Mar 25;1382:37-44
pubmed: 21276428
Brain Pathol. 2013 Mar;23(2):154-64
pubmed: 22897695
J Neuroimmunol. 2011 Aug 15;237(1-2):73-9
pubmed: 21737148
Science. 2019 Jan 25;363(6425):
pubmed: 30679343
Brain. 2020 May 1;143(5):1476-1497
pubmed: 32355963
Biophys J. 2010 Oct 6;99(7):2116-24
pubmed: 20923645
Sci Signal. 2018 Dec 11;11(560):
pubmed: 30538177
Acta Neuropathol. 2017 Nov;134(5):789-808
pubmed: 28725967
Cell. 2020 Apr 30;181(3):557-573.e18
pubmed: 32259484
Nat Neurosci. 2016 May 26;19(6):771-83
pubmed: 27227366
Ann N Y Acad Sci. 2000;920:16-27
pubmed: 11193145
J Alzheimers Dis. 2004 Aug;6(4):435-42; discussion 443-9
pubmed: 15345814
J Exp Med. 2020 Apr 6;217(4):
pubmed: 32211826
J Cereb Blood Flow Metab. 2018 Apr;38(4):669-686
pubmed: 29283289
J Neurochem. 2019 Sep;150(5):522-534
pubmed: 31254394
Ann Neurol. 2003 Nov;54(5):599-604
pubmed: 14595649
Glia. 2005 Sep;51(4):297-305
pubmed: 15846794
Acta Neuropathol. 2000 Oct;100(4):395-402
pubmed: 10985698
Peptides. 2014 Dec;62:197-202
pubmed: 25278492
J Neurochem. 2016 Oct;139 Suppl 1:256-274
pubmed: 26924014
Br Med J. 1966 Aug 27;2(5512):487-90
pubmed: 5913081
Biochim Biophys Acta. 2016 Mar;1862(3):461-71
pubmed: 26527183
Nature. 2015 Jun 18;522(7556):340-4
pubmed: 26061766
Int J Clin Exp Pathol. 2019 May 01;12(5):1757-1763
pubmed: 31933994
J Neurochem. 2007 Dec;103(6):2401-7
pubmed: 17883396
Arterioscler Thromb Vasc Biol. 2006 May;26(5):1002-7
pubmed: 16469951
Cell Rep. 2016 Aug 9;16(6):1749-1761
pubmed: 27477286
Transl Neurodegener. 2019 Mar 1;8:7
pubmed: 30867902
Dis Model Mech. 2017 Sep 1;10(9):1075-1087
pubmed: 28883016
Neurobiol Aging. 2008 Nov;29(11):1690-701
pubmed: 17537546
Parkinsons Dis. 2015;2015:108029
pubmed: 25918668
Neurochem Res. 2010 Apr;35(4):540-7
pubmed: 19924532
J Chem Neuroanat. 2011 Dec;42(4):242-8
pubmed: 21167933
J Neurosci. 2020 Nov 4;40(45):8618-8628
pubmed: 33046546
Immunity. 2018 Feb 20;48(2):380-395.e6
pubmed: 29426702
J Biol Chem. 2003 Dec 19;278(51):51743-8
pubmed: 14525976
Neurosci Lett. 1994 Oct 24;180(2):147-50
pubmed: 7700568
Cardiovasc Res. 2010 Jul 15;87(2):243-53
pubmed: 20299335
Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):4087-92
pubmed: 23431141
Brain. 2020 May 1;143(5):1462-1475
pubmed: 32380543
Neurodegener Dis. 2011;8(4):221-9
pubmed: 21212632
J Neuroimmune Pharmacol. 2013 Mar;8(1):94-117
pubmed: 23054368
Neuropathol Appl Neurobiol. 2016 Feb;42(1):77-94
pubmed: 26613567
Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11282-6
pubmed: 8248242
Curr Aging Sci. 2017;10(3):177-184
pubmed: 28042771
Nature. 2018 Aug;560(7717):185-191
pubmed: 30046111
Microvasc Res. 2019 Jul;124:61-66
pubmed: 30885616
Brain Res. 2015 Dec 2;1628(Pt B):247-253
pubmed: 26080075
Brain Pathol. 2018 Nov;28(6):875-888
pubmed: 29330884
Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):1074-9
pubmed: 26755608
Neurobiol Dis. 2020 Apr;137:104722
pubmed: 31926295
Neurochem Res. 2007 Dec;32(12):2032-45
pubmed: 17457674
Front Mol Neurosci. 2018 Apr 27;11:144
pubmed: 29755317
J Neural Transm (Vienna). 2012 Jan;119(1):59-71
pubmed: 21748523
Prog Neurobiol. 2002 Dec;68(5):325-40
pubmed: 12531233
J Neurosci. 2004 Dec 8;24(49):11165-70
pubmed: 15590933
Neurodegeneration. 1995 Sep;4(3):257-69
pubmed: 8581558
Fluids Barriers CNS. 2014 Jul 31;11:17
pubmed: 25093076
Hum Mol Genet. 2019 Jan 1;28(1):31-50
pubmed: 30219847
Nat Commun. 2019 Dec 20;10(1):5816
pubmed: 31862977
Neurodegener Dis. 2008;5(2):55-9
pubmed: 18182779
Brain Res. 2012 Oct 2;1476:183-202
pubmed: 22560500
Acta Neuropathol. 2018 Mar;135(3):311-336
pubmed: 29411111
Nat Med. 1998 Nov;4(11):1318-20
pubmed: 9809558
J Neuroinflammation. 2020 Sep 17;17(1):272
pubmed: 32943057
Biochemistry. 1996 Oct 29;35(43):13709-15
pubmed: 8901511
J Cereb Blood Flow Metab. 2015 May;35(5):747-50
pubmed: 25757748
Brain. 2016 Feb;139(Pt 2):481-94
pubmed: 26647156
Genes (Basel). 2017 Dec 08;8(12):
pubmed: 29292725
PLoS One. 2016 Sep 13;11(9):e0162717
pubmed: 27622765
Alzheimers Res Ther. 2014 May 07;6(3):25
pubmed: 24987465
Redox Biol. 2018 Apr;14:600-608
pubmed: 29154191
Immunity. 2016 May 17;44(5):1162-76
pubmed: 27156384
Acta Neuropathol Commun. 2018 Aug 9;6(1):76
pubmed: 30092836
Nat Commun. 2020 Apr 20;11(1):1875
pubmed: 32313102
J Cereb Blood Flow Metab. 2010 May;30(5):1031-43
pubmed: 20087368
Cell Stress. 2019 Sep 25;3(11):330-347
pubmed: 31799500
Nat Neurosci. 2019 Jun;22(6):1021-1035
pubmed: 31061494
Nat Rev Neurol. 2016 Aug;12(8):439-54
pubmed: 27364743
Front Cell Neurosci. 2018 Aug 06;12:247
pubmed: 30127724
J Biol Chem. 2001 Jan 26;276(4):2380-6
pubmed: 11060312
J Am Chem Soc. 2015 Apr 22;137(15):5041-52
pubmed: 25768729
Eur J Neurosci. 2006 Dec;24(11):3153-62
pubmed: 17156376
Arterioscler Thromb Vasc Biol. 2019 Nov;39(11):2240-2247
pubmed: 31510792
J Neuroinflammation. 2011 Nov 06;8:154
pubmed: 22053982
Oxid Med Cell Longev. 2019 Nov 23;2019:4246350
pubmed: 31871549
FASEB J. 2005 Apr;19(6):533-42
pubmed: 15791003
Am J Pathol. 2006 Mar;168(3):822-34
pubmed: 16507898
Acta Neuropathol. 2019 Feb;137(2):359-361
pubmed: 30506319
Biochemistry. 2009 Feb 10;48(5):1077-83
pubmed: 19146388
Stem Cell Investig. 2019 Apr 19;6:10
pubmed: 31119148
Int J Mol Sci. 2018 Jan 17;19(1):
pubmed: 29342116
Lancet Neurol. 2019 May;18(5):459-480
pubmed: 30879893
Acta Neuropathol. 2019 Jul;138(1):1-21
pubmed: 30798354
Molecules. 2019 Jan 15;24(2):
pubmed: 30650656
Eur J Neurosci. 2004 Mar;19(6):1494-504
pubmed: 15066146
J Biol Chem. 2010 Jul 9;285(28):21416-25
pubmed: 20448034
J Neuropathol Exp Neurol. 2009 Feb;68(2):159-67
pubmed: 19151626
Trends Neurosci. 2017 Jan;40(1):4-14
pubmed: 27894611
Sci Rep. 2021 Jan 13;11(1):1120
pubmed: 33441868
J Am Chem Soc. 2005 Jan 19;127(2):476-7
pubmed: 15643843
Acta Neuropathol. 2017 Oct;134(4):629-653
pubmed: 28527044
Neural Plast. 2017;2017:5012129
pubmed: 28133550
Neurobiol Dis. 2006 Feb;21(2):404-12
pubmed: 16182554