SARS-CoV-2 infection exacerbates the cellular pathology of Parkinson’s disease in human dopaminergic neurons and a mouse model
Bina Lee, Ha Nyeoung Choi, Young Se Hyun, Myungjun Ko, Hye Min Seong, Min Gi Jo, Seon‐Hee Kim, Chieun Song, Subeen Yoon, Jiwoo Choi, Jeong Hee Kim, Minkyeong Kim, Min Young Lee, Sang Won Park, Hye Jung Kim, Seong-Jae Kim, Do Sik Moon, Sun Lee, Jae‐Hoon Park, Seung Geun Yeo, Richard G. Everson, Young J. Kim, Young Jin Kim, Kyung‐Wook Hong, In‐Soon Roh, Kwang‐Soo Lyoo, Yong Jun Kim, 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.