The Expression and Functionality of CB 1 R-NMDAR Complexes Are Decreased in A Parkinson's Disease Model.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Parkinson Disease*/metabolism; Animals ; Mice ; alpha-Synuclein/metabolism ; Neurons/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Signal Transduction

One of the hallmarks of Parkinson's disease (PD) is the alteration in the expression and function of NMDA receptor (NMDAR) and cannabinoid receptor 1 (CB 1 R). The presence of CB 1 R-NMDAR complexes has been described in neuronal primary cultures. The activation of CB 1 R in CB 1 R-NMDAR complexes was suggested to counteract the detrimental NMDAR overactivation in an AD mice model. Thus, we aimed to explore the role of this receptor complex in PD. By using Bioluminescence Resonance Energy Transfer (BRET) assay, it was demonstrated that α-synuclein induces a reorganization of the CB 1 R-NMDAR complex in transfected HEK-293T cells. Moreover, α-synuclein treatment induced a decrease in the cAMP and MAP kinase (MAPK) signaling of both CB 1 R and NMDAR not only in transfected cells but also in neuronal primary cultures. Finally, the interaction between CB 1 R and NMDAR was studied by Proximity Ligation Assay (PLA) in neuronal primary cultures, where it was observed that the expression of CB 1 R-NMDAR complexes was decreased upon α-synuclein treatment. These results point to a role of CB 1 R-NMDAR complexes as a new therapeutic target in Parkinson's disease.

Oncotarget. 2018 Feb 6;9(17):13593-13611. (PMID: 29568380)
Mov Disord. 2016 Feb;31(2):161-8. (PMID: 26347034)
Front Cell Neurosci. 2015 Jul 06;9:245. (PMID: 26217176)
Mov Disord. 2011 Aug 1;26(9):1616. (PMID: 21938766)
Acta Neuropathol. 2013 Oct;126(4):555-73. (PMID: 23925565)
Acta Neuropathol Commun. 2014 Aug 06;2:88. (PMID: 25095794)
Science. 1997 Jun 27;276(5321):2045-7. (PMID: 9197268)
Eur J Neurosci. 2001 Dec;14(11):1827-32. (PMID: 11860478)
Nat Rev Neurosci. 2010 Oct;11(10):682-96. (PMID: 20842175)
Curr Med Chem. 2010;17(14):1382-93. (PMID: 20166926)
Nat Rev Neurosci. 2013 Jun;14(6):383-400. (PMID: 23686171)
Cell Death Dis. 2023 Mar 1;14(3):176. (PMID: 36859484)
Lancet Neurol. 2009 Apr;8(4):382-97. (PMID: 19296921)
Neuroscience. 2014 Apr 18;265:245-52. (PMID: 24486947)
J Mol Biol. 2023 Jan 15;435(1):167775. (PMID: 35931109)
Adv Exp Med Biol. 2021;1264:81-92. (PMID: 33332005)
Neurotoxicology. 2018 Mar;65:38-43. (PMID: 29366825)
Ann Neurol. 2014 Mar;75(3):351-62. (PMID: 24243558)
Acta Neuropathol. 2016 Apr;131(4):539-48. (PMID: 26820848)
Cell. 2010 Mar 19;140(6):918-34. (PMID: 20303880)
PLoS One. 2017 Aug 30;12(8):e0182887. (PMID: 28854243)
Front Neuroendocrinol. 2014 Aug;35(3):370-84. (PMID: 24607323)
Alzheimers Res Ther. 2021 Nov 8;13(1):184. (PMID: 34749800)
Mol Pharmacol. 2000 Feb;57(2):342-52. (PMID: 10648644)
J Neurosci. 2007 Aug 22;27(34):9220-32. (PMID: 17715357)
Neurobiol Aging. 2012 Mar;33(3):620.e1-8. (PMID: 21459482)
Nature. 1993 Jan 7;361(6407):31-9. (PMID: 8421494)
Mol Neurobiol. 2017 Aug;54(6):4537-4550. (PMID: 27370794)
Brain Behav Immun. 2018 Jan;67:139-151. (PMID: 28843453)
Brain Res. 1998 Nov 30;813(1):150-9. (PMID: 9824689)
J Exp Med. 2012 May 7;209(5):975-86. (PMID: 22508839)
J Neural Transm (Vienna). 2003 Nov;110(11):1279-88. (PMID: 14628192)
J Neural Transm Suppl. 2009;(73):269-75. (PMID: 20411785)
Lancet Neurol. 2016 Nov;15(12):1257-1272. (PMID: 27751556)
Neuropharmacology. 2020 Sep 1;174:108136. (PMID: 32474027)
Nature. 1997 Aug 28;388(6645):839-40. (PMID: 9278044)
Nat Genet. 2009 Dec;41(12):1308-12. (PMID: 19915575)
Mov Disord. 2022 Aug;37(8):1673-1682. (PMID: 35674270)
Biol Psychiatry. 2016 Apr 1;79(7):516-25. (PMID: 26698193)
Neurobiol Dis. 2018 Jan;109(Pt B):219-225. (PMID: 28323023)
Science. 2000 Feb 18;287(5456):1265-9. (PMID: 10678833)
Molecules. 2022 Jan 14;27(2):. (PMID: 35056822)
J Neuroinflammation. 2018 May 1;15(1):129. (PMID: 29716614)
EMBO J. 2016 Oct 4;35(19):2120-2138. (PMID: 27550960)
Nat Rev Dis Primers. 2017 Mar 23;3:17013. (PMID: 28332488)
Front Mol Neurosci. 2018 Aug 28;11:273. (PMID: 30233307)
Brain. 2019 May 1;142(5):1365-1385. (PMID: 30927362)
Nature. 2013 Jul 18;499(7458):295-300. (PMID: 23868258)
Cells. 2020 Apr 26;9(5):. (PMID: 32357548)
Mov Disord. 1998 May;13(3):414-7. (PMID: 9613730)
Nat Neurosci. 2017 Nov;20(11):1569-1579. (PMID: 28945221)
Life Sci. 2000;66(6):485-94. (PMID: 10794065)
Neurobiol Dis. 2012 Mar;45(3):939-53. (PMID: 22182688)
J Neurosci Res. 2018 Jul;96(7):1324-1335. (PMID: 29577359)
Cold Spring Harb Perspect Med. 2012 Jan;2(1):a008888. (PMID: 22315721)
Mov Disord. 2001 May;16(3):448-58. (PMID: 11391738)
Biol Psychiatry. 2016 Mar 1;79(5):402-414. (PMID: 26392130)
J Neurosci. 2014 Aug 6;34(32):10603-15. (PMID: 25100594)
Neuron. 2011 Oct 6;72(1):57-71. (PMID: 21982369)
J Neurosci. 2002 Aug 15;22(16):6900-7. (PMID: 12177188)
Drug Des Devel Ther. 2014 Jan 17;8:165-73. (PMID: 24465126)
Mov Disord. 2010 May 15;25(7):920-4. (PMID: 20461809)

PID 2020-113430RB-I00 Spanish Ministry of Science and Innovation; PID 2021-126600OB-I00 Spanish Ministry of Science and Innovation

Keywords: NMDA receptor; Parkinson’s disease; cannabinoid receptor 1; receptor heteromer; α-synuclein

0 (alpha-Synuclein)
0 (Gprin1 protein, mouse)
0 (Receptors, N-Methyl-D-Aspartate)
0 (CNR1 protein, mouse)

Date Created: 20240313 Date Completed: 20240314 Latest Revision: 20240320

20240320

PMC10931566

10.3390/ijms25053021

38474266