Reduction of Lewy Body Pathology by Oral Cinnamon.
A53T mice
Cinnamon
Glial activation
Sodium benzoate
α-synucleinopathy
Journal
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
ISSN: 1557-1904
Titre abrégé: J Neuroimmune Pharmacol
Pays: United States
ID NLM: 101256586
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
21
08
2020
accepted:
31
08
2020
pubmed:
6
9
2020
medline:
18
1
2022
entrez:
5
9
2020
Statut:
ppublish
Résumé
α-Synucleinopathies in a broader sense comprise of several neurodegenerative disorders that primarily include Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). These disorders are well characterized by the accumulation of aggregated insoluble α-synuclein (α-syn) protein known as Lewy bodies. Till date no effective cure is available to reduce the burden of Lewy body. The present investigation underlines the importance of a naturally used spice and flavoring agent viz. cinnamon in reducing α-syn deposits in transgenic mice expressing mutant A53T human α-syn. Upon oral administration, cinnamon markedly reduced the level of insoluble α-syn in nigra, hippocampus and brain stem of A53T mice. We also demonstrated that sodium benzoate (NaB), a metabolite of cinnamon, a widely used food additive and a FDA-approved drug for glycine encephalopathy, was also capable of reducing α-syn deposits in A53T mice. In addition, both cinnamon and NaB treatments showed improvement in their motor and cognitive functions. Glial activation plays an important role in the pathogenesis of various neurodegenerative disorders including PD, DLB and MSA, and we found suppression of microglial and astroglial activation in the nigra of A53T mice upon cinnamon treatment. Moreover, neuroprotective proteins like DJ-1 and Parkin are known to reduce the formation of Lewy bodies in the CNS. Accordingly, we observed upregulation and/or normalization of DJ-1 and Parkin in the nigra of A53T mice by treatment with cinnamon and NaB. Together, these results highlight a new therapeutic property of cinnamon and suggest that cinnamon and NaB may be used to halt the progression of α-synucleinopathies.Graphical Abstract.
Identifiants
pubmed: 32889602
doi: 10.1007/s11481-020-09955-2
pii: 10.1007/s11481-020-09955-2
pmc: PMC7933354
mid: NIHMS1626617
doi:
Substances chimiques
alpha-Synuclein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
592-608Subventions
Organisme : BLRD VA
ID : I01 BX005002
Pays : United States
Organisme : BLRD VA
ID : I01 BX003033
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS108025
Pays : United States
Organisme : BLRD VA
ID : IK6 BX004982
Pays : United States
Informations de copyright
© 2020. Springer Science+Business Media, LLC, part of Springer Nature.
Références
Nat Chem Biol. 2016 Dec;12(12):1075-1083
pubmed: 27748752
J Parkinsons Dis. 2013 Jan 1;3(3):255-69
pubmed: 23948989
Exp Neurol. 2008 Aug;212(2):258-60
pubmed: 18538324
J Neuroimmune Pharmacol. 2014 Sep;9(4):569-81
pubmed: 24946862
Free Radic Biol Med. 2009 Nov 15;47(10):1354-61
pubmed: 19686841
J Immunol. 2007 Jul 1;179(1):275-83
pubmed: 17579047
Neuropathol Appl Neurobiol. 2021 Feb;47(1):43-60
pubmed: 32696999
Science. 1997 Jun 27;276(5321):2045-7
pubmed: 9197268
Anal Chem. 2009 Sep 15;81(18):7823-8
pubmed: 19697948
Free Radic Biol Med. 2009 May 15;46(10):1328-37
pubmed: 19248830
Neural Regen Res. 2015 Jan;10(1):30-2
pubmed: 25788911
Immunopharmacol Immunotoxicol. 2011 Dec;33(4):586-93
pubmed: 21425926
J Neurochem. 2017 Dec;143(5):584-594
pubmed: 28921554
J Neuroimmune Pharmacol. 2012 Jun;7(2):424-35
pubmed: 21701815
J Clin Invest. 2020 Aug 3;130(8):4195-4212
pubmed: 32597830
J Mult Scler (Foster City). 2015;2(3):1000149
pubmed: 26380380
J Neuroimmune Pharmacol. 2013 Jun;8(3):739-55
pubmed: 23475543
Proc Natl Acad Sci U S A. 2015 Jul 7;112(27):8445-50
pubmed: 26080426
J Parkinsons Dis. 2016;6(1):39-51
pubmed: 27003784
PLoS One. 2014 Dec 08;9(12):e114216
pubmed: 25486126
Nat Commun. 2020 Mar 13;11(1):1386
pubmed: 32170061
J Exp Med. 2012 May 7;209(5):975-86
pubmed: 22508839
Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):E6506-E6515
pubmed: 27708160
Nature. 1997 Aug 28;388(6645):839-40
pubmed: 9278044
PLoS One. 2014 May 06;9(5):e96801
pubmed: 24802416
J Neuroinflammation. 2018 May 1;15(1):129
pubmed: 29716614
Glia. 2002 Nov;40(2):164-74
pubmed: 12379904
J Neurosci. 2009 Oct 28;29(43):13543-56
pubmed: 19864567
JCI Insight. 2020 May 21;5(10):
pubmed: 32315292
Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18754-9
pubmed: 18000063
Autophagy. 2020 Sep;16(9):1718-1720
pubmed: 32453651
Neurobiol Dis. 2010 Mar;37(3):510-8
pubmed: 19913097
N Engl J Med. 1998 Oct 8;339(15):1044-53
pubmed: 9761807
PLoS One. 2010 Apr 08;5(4):e9956
pubmed: 20386702
Cell Death Dis. 2014 Jul 24;5:e1350
pubmed: 25058424
J Inherit Metab Dis. 2000 Feb;23(1):22-6
pubmed: 10682305
J Biol Chem. 2004 Mar 26;279(13):12924-34
pubmed: 14711827
J Neuroimmune Pharmacol. 2019 Sep;14(3):503-518
pubmed: 31119595
Mol Neurodegener. 2010 Nov 04;5:47
pubmed: 21050448
J Biol Chem. 2006 Mar 31;281(13):8591-9
pubmed: 16455660
PLoS One. 2015 Jun 23;10(6):e0130398
pubmed: 26102198
J Biol Chem. 2003 Apr 4;278(14):11753-9
pubmed: 12551928
Prog Neurobiol. 2017 Apr;151:175-236
pubmed: 27013075
Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10907-12
pubmed: 18669654
J Biol Chem. 2016 Jul 15;291(29):15267-81
pubmed: 27226559
J Neurol. 2003 Oct;250 Suppl 3:III15-24
pubmed: 14579120
PLoS One. 2015 Jan 08;10(1):e0116566
pubmed: 25569428
PLoS One. 2017 Jun 27;12(6):e0180602
pubmed: 28654697
Semin Cell Dev Biol. 2020 Mar;99:172-182
pubmed: 31132469
Eur J Neurol. 2020 Jan;27(1):27-42
pubmed: 31631455
J Biol Chem. 2002 Dec 13;277(50):49071-6
pubmed: 12377775
Aging (Albany NY). 2020 Jul 24;12(14):14232-14243
pubmed: 32706757
Appl Environ Microbiol. 2008 May;74(10):3284-90
pubmed: 18344329
J Biol Chem. 2006 Oct 6;281(40):29739-52
pubmed: 16847063
Int J Mol Sci. 2017 Mar 09;18(3):
pubmed: 28282924