고명준 (University of California, Los Angeles)

한빛사논문

조회243

고명준Myungjun Ko

University of California, Los Angeles

Cell Rep. Med., May 10 2024, S2666-3791(24)00262-3 | https://doi.org/10.1016/j.xcrm.2024.101570 SARS-CoV-2 infection exacerbates the cellular pathology of Parkinson's disease in human dopaminergic neurons and a mouse model

Bina Lee ^1,16, Ha Nyeoung Choi ^1,2,16, Young Hyun Che ^3,4,16, Myungjun Ko ^5,16, Hye Min Seong⁶, Min Gi Jo ^1,4, Seon-Hee Kim¹, Chieun Song ⁶, Subeen Yoon^3,4, Jiwoo Choi ^3,4, Jeong Hee Kim ^3,4, Minkyeong Kim⁷, Min Young Lee ⁸, Sang Won Park ^1,2, Hye Jung Kim ^1,2, Seong Jae Kim ⁶, Do Sik Moon ⁹, Sun Lee ^4,10, Jae-Hoon Park ⁴, Seung-Geun Yeo ¹¹, Richard G. Everson ⁵, Young Jin Kim^1,2, Kyung-Wook Hong ¹², In-Soon Roh ¹³, Kwang-Soo Lyoo ¹⁴, Yong Jun Kim^3,4,10,15,17, Seung Pil Yun ^1,2

¹Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea

²Department of Convergence Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea

³Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea

⁴Department of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea

⁵Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA

⁶Department of Ophthalmology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea

⁷Department of Neurology, Gyeongsang National University Hospital, Jinju 52727, Republic of Korea

⁸College of Pharmacy, Research Institute of Pharmaceutical Sciences, BK21 FOUR ERGID, Vessel-Organ Interaction Research Center (MRC), Kyungpook National University, Daegu 4156, Republic of Korea

⁹Department of Pulmonology and Critical Care Medicine, Chosun University Hospital, Gwangju 61453, Republic of Korea

¹⁰Research Center, TissueIn, Inc., Seoul 06158, Republic of Korea

¹¹Department of Otorhinolaryngology - Head and Neck Surgery, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea

¹²Division of Infectious Diseases, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Republic of Korea

¹³Division of Foreign Animal Disease, Animal and Plant Quarantine Agency, Gimcheon-si, Gyeongsangbuk-do 39660, Republic of Korea

¹⁴Department of Veterinary Nursing, College of Health Sciences, Wonkwang University, Iksan 54538, Republic of Korea

¹⁵KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea

¹⁶These authors contributed equally

¹⁷Lead contact

Corresponding authors: Kwang-Soo Lyoo, Yong Jun Kim, Seung Pil Yun

Abstract

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.

논문정보

형식Research article
게재일2024년 05월 (BRIC 등록일 2024-05-16)
연구진국내(교신)+국외 연구진
분야 의약학 > 분자세포의학

댓글 작성 로그인

CV 열람하기

연락처 보기