SARS-CoV-2 Proteins Interact with Alpha Synuclein and Induce Lewy Body-like Pathology In Vitro

Growing cases of patients reported have shown a potential relationship between (severe acute respiratory syndrome coronavirus 2) SARS-CoV-2 infection and Parkinson’s disease (PD). However, it is unclear whether there is a molecular link between these two diseases. Alpha-synuclein (α-Syn), an aggrega...

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Main Authors: Zhengcun Wu, Xiuao Zhang, Zhangqiong Huang, Kaili Ma
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/6/3394
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author Zhengcun Wu
Xiuao Zhang
Zhangqiong Huang
Kaili Ma
author_facet Zhengcun Wu
Xiuao Zhang
Zhangqiong Huang
Kaili Ma
author_sort Zhengcun Wu
collection DOAJ
description Growing cases of patients reported have shown a potential relationship between (severe acute respiratory syndrome coronavirus 2) SARS-CoV-2 infection and Parkinson’s disease (PD). However, it is unclear whether there is a molecular link between these two diseases. Alpha-synuclein (α-Syn), an aggregation-prone protein, is considered a crucial factor in PD pathology. In this study, bioinformatics analysis confirmed favorable binding affinity between α-Syn and SARS-CoV-2 spike (S) protein and nucleocapsid (N) protein, and direct interactions were further verified in HEK293 cells. The expression of α-Syn was upregulated and its aggregation was accelerated by S protein and N protein. It was noticed that SARS-CoV-2 proteins caused Lewy-like pathology in the presence of α-Syn overexpression. By confirming that SARS-CoV-2 proteins directly interact with α-Syn, our study offered new insights into the mechanism underlying the development of PD on the background of COVID-19.
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spelling doaj.art-45cf2d0e5cba4d85b5edee016ddb6f462023-11-24T01:38:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01236339410.3390/ijms23063394SARS-CoV-2 Proteins Interact with Alpha Synuclein and Induce Lewy Body-like Pathology In VitroZhengcun Wu0Xiuao Zhang1Zhangqiong Huang2Kaili Ma3Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, ChinaInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, ChinaGrowing cases of patients reported have shown a potential relationship between (severe acute respiratory syndrome coronavirus 2) SARS-CoV-2 infection and Parkinson’s disease (PD). However, it is unclear whether there is a molecular link between these two diseases. Alpha-synuclein (α-Syn), an aggregation-prone protein, is considered a crucial factor in PD pathology. In this study, bioinformatics analysis confirmed favorable binding affinity between α-Syn and SARS-CoV-2 spike (S) protein and nucleocapsid (N) protein, and direct interactions were further verified in HEK293 cells. The expression of α-Syn was upregulated and its aggregation was accelerated by S protein and N protein. It was noticed that SARS-CoV-2 proteins caused Lewy-like pathology in the presence of α-Syn overexpression. By confirming that SARS-CoV-2 proteins directly interact with α-Syn, our study offered new insights into the mechanism underlying the development of PD on the background of COVID-19.https://www.mdpi.com/1422-0067/23/6/3394Parkinson’s diseaseSARS-CoV-2alpha-synucleinspike proteinnucleocapsid protein
spellingShingle Zhengcun Wu
Xiuao Zhang
Zhangqiong Huang
Kaili Ma
SARS-CoV-2 Proteins Interact with Alpha Synuclein and Induce Lewy Body-like Pathology In Vitro
International Journal of Molecular Sciences
Parkinson’s disease
SARS-CoV-2
alpha-synuclein
spike protein
nucleocapsid protein
title SARS-CoV-2 Proteins Interact with Alpha Synuclein and Induce Lewy Body-like Pathology In Vitro
title_full SARS-CoV-2 Proteins Interact with Alpha Synuclein and Induce Lewy Body-like Pathology In Vitro
title_fullStr SARS-CoV-2 Proteins Interact with Alpha Synuclein and Induce Lewy Body-like Pathology In Vitro
title_full_unstemmed SARS-CoV-2 Proteins Interact with Alpha Synuclein and Induce Lewy Body-like Pathology In Vitro
title_short SARS-CoV-2 Proteins Interact with Alpha Synuclein and Induce Lewy Body-like Pathology In Vitro
title_sort sars cov 2 proteins interact with alpha synuclein and induce lewy body like pathology in vitro
topic Parkinson’s disease
SARS-CoV-2
alpha-synuclein
spike protein
nucleocapsid protein
url https://www.mdpi.com/1422-0067/23/6/3394
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AT xiuaozhang sarscov2proteinsinteractwithalphasynucleinandinducelewybodylikepathologyinvitro
AT zhangqionghuang sarscov2proteinsinteractwithalphasynucleinandinducelewybodylikepathologyinvitro
AT kailima sarscov2proteinsinteractwithalphasynucleinandinducelewybodylikepathologyinvitro