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SARS-CoV-2 infection exacerbates the cellular pathology of Parkinson's disease in human dopaminergic neurons and a mouse model.

التفاصيل البيبلوغرافية
العنوان: SARS-CoV-2 infection exacerbates the cellular pathology of Parkinson's disease in human dopaminergic neurons and a mouse model.
المؤلفون: Lee B; Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea., Choi HN; Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea; Department of Convergence Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea., Che YH; Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea., Ko M; Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Seong HM; Department of Ophthalmology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea., Jo MG; Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea; Department of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea., Kim SH; Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea., Song C; Department of Ophthalmology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea., Yoon S; Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea., Choi J; Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea., Kim JH; Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea., Kim M; Department of Neurology, Gyeongsang National University Hospital, Jinju 52727, Republic of Korea., Lee MY; College of Pharmacy, Research Institute of Pharmaceutical Sciences, BK21 FOUR ERGID, Vessel-Organ Interaction Research Center (MRC), Kyungpook National University, Daegu 4156, Republic of Korea., Park SW; Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea; Department of Convergence Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea., Kim HJ; Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea; Department of Convergence Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea., Kim SJ; Department of Ophthalmology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea., Moon DS; Department of Pulmonology and Critical Care Medicine, Chosun University Hospital, Gwangju 61453, Republic of Korea., Lee S; Department of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; Research Center, TissueIn, Inc., Seoul 06158, Republic of Korea., Park JH; Department of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea., Yeo SG; Department of Otorhinolaryngology - Head and Neck Surgery, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea., Everson RG; Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA., Kim YJ; Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea; Department of Convergence Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea., Hong KW; Division of Infectious Diseases, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Republic of Korea., Roh IS; Division of Foreign Animal Disease, Animal and Plant Quarantine Agency, Gimcheon-si, Gyeongsangbuk-do 39660, Republic of Korea., Lyoo KS; Department of Veterinary Nursing, College of Health Sciences, Wonkwang University, Iksan 54538, Republic of Korea. Electronic address: lks1314@wku.ac.kr., Kim YJ; Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; Department of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea; Research Center, TissueIn, Inc., Seoul 06158, Republic of Korea; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea. Electronic address: yjkim1@khu.ac.kr., Yun SP; Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea; Department of Convergence Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea. Electronic address: spyun@gnu.ac.kr.
المصدر: Cell reports. Medicine [Cell Rep Med] 2024 May 21; Vol. 5 (5), pp. 101570. Date of Electronic Publication: 2024 May 14.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101766894 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2666-3791 (Electronic) Linking ISSN: 26663791 NLM ISO Abbreviation: Cell Rep Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Cambridge, MA] : Cell Press, [2020]-
مواضيع طبية MeSH: Dopaminergic Neurons*/pathology , Dopaminergic Neurons*/metabolism , Dopaminergic Neurons*/virology , COVID-19*/pathology , COVID-19*/virology , Parkinson Disease*/pathology , Parkinson Disease*/virology , SARS-CoV-2* , Disease Models, Animal* , Mice, Transgenic* , Angiotensin-Converting Enzyme 2*/metabolism , Angiotensin-Converting Enzyme 2*/genetics, Animals ; Humans ; Mice ; Microglia/pathology ; Microglia/metabolism ; Microglia/virology ; Human Embryonic Stem Cells/metabolism ; Astrocytes/pathology ; Astrocytes/virology ; Astrocytes/metabolism ; Brain/pathology ; Brain/virology
مستخلص: While an association between Parkinson's disease (PD) and viral infections has been recognized, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on PD progression remains unclear. Here, we demonstrate that SARS-CoV-2 infection heightens the risk of PD using human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons and a human angiotensin-converting enzyme 2 (hACE2) transgenic (Tg) mouse model. Our findings reveal that SARS-CoV-2 infection exacerbates PD susceptibility and cellular toxicity in DA neurons pre-treated with human preformed fibrils (hPFFs). Additionally, nasally delivered SARS-CoV-2 infects DA neurons in hACE2 Tg mice, aggravating the damage initiated by hPFFs. Mice infected with SARS-CoV-2 display persisting neuroinflammation even after the virus is no longer detectable in the brain. A comprehensive analysis suggests that the inflammatory response mediated by astrocytes and microglia could contribute to increased PD susceptibility associated with SARS-CoV-2. These findings advance our understanding of the potential long-term effects of SARS-CoV-2 infection on the progression of PD.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
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فهرسة مساهمة: Keywords: COVID-19 sequalae; DA neuron; PD; Parkinson’s disease; SARS-CoV-2; disease modeling; dopaminergic neuron; hACE2 transgenic mouse; neuroinflammation; neurological sequelae
المشرفين على المادة: EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
EC 3.4.17.23 (ACE2 protein, human)
تواريخ الأحداث: Date Created: 20240515 Date Completed: 20240522 Latest Revision: 20240607
رمز التحديث: 20240607
مُعرف محوري في PubMed: PMC11148862
DOI: 10.1016/j.xcrm.2024.101570
PMID: 38749422
قاعدة البيانات: MEDLINE
الوصف
تدمد:2666-3791
DOI:10.1016/j.xcrm.2024.101570