SARS-CoV-2 infection exacerbates the cellular pathology of Parkinson's disease in human dopaminergic neurons and a mouse modelopen access
- Authors
- Lee, Bina; Choi, Ha Nyeoung; Che, Young Hyun; Ko, Myungjun; Seong, Hye Min; Jo, Min Gi; Kim, Seon-Hee; Song, Chieun; Yoon, Subeen; Choi, Jiwoo; Kim, Jeong Hee; Kim, Minkyeong; Lee, Min Young; Park, Sang Won; Kim, Hye Jung; Kim, Seong Jae; Moon, Do Sik; Lee, Sun; Park, Jae-Hoon; Yeo, Seung-Geun; Everson, Richard G.; Kim, Young Jin; Hong, Kyung-Wook; Roh, In-Soon; Lyoo, Kwang-Soo; Kim, Yong Jun; Yun, Seung Pil
- Issue Date
- May-2024
- Publisher
- Cell Press
- Keywords
- COVID-19 sequalae; DA neuron; disease modeling; dopaminergic neuron; hACE2 transgenic mouse; neuroinflammation; neurological sequelae; Parkinson's disease; PD; SARS-CoV-2
- Citation
- Cell Reports Medicine, v.5, no.5
- Indexed
- SCIE
SCOPUS
- Journal Title
- Cell Reports Medicine
- Volume
- 5
- Number
- 5
- URI
- https://scholarworks.gnu.ac.kr/handle/sw.gnu/70669
- DOI
- 10.1016/j.xcrm.2024.101570
- ISSN
- 2666-3791
2666-3791
- 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. © 2024 The Author(s)
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