tetano
Editor, Senior Moderator
Cell Rep Med
. 2024 May 10:101570.
doi: 10.1016/j.xcrm.2024.101570. Online ahead of print. SARS-CoV-2 infection exacerbates the cellular pathology of Parkinson's disease in human dopaminergic neurons and a mouse model
Bina Lee[SUP] 1 [/SUP], Ha Nyeoung Choi[SUP] 2 [/SUP], Young Hyun Che[SUP] 3 [/SUP], Myungjun Ko[SUP] 4 [/SUP], Hye Min Seong[SUP] 5 [/SUP], Min Gi Jo[SUP] 6 [/SUP], Seon-Hee Kim[SUP] 1 [/SUP], Chieun Song[SUP] 5 [/SUP], Subeen Yoon[SUP] 3 [/SUP], Jiwoo Choi[SUP] 3 [/SUP], Jeong Hee Kim[SUP] 3 [/SUP], Minkyeong Kim[SUP] 7 [/SUP], Min Young Lee[SUP] 8 [/SUP], Sang Won Park[SUP] 2 [/SUP], Hye Jung Kim[SUP] 2 [/SUP], Seong Jae Kim[SUP] 5 [/SUP], Do Sik Moon[SUP] 9 [/SUP], Sun Lee[SUP] 10 [/SUP], Jae-Hoon Park[SUP] 11 [/SUP], Seung-Geun Yeo[SUP] 12 [/SUP], Richard G Everson[SUP] 4 [/SUP], Young Jin Kim[SUP] 2 [/SUP], Kyung-Wook Hong[SUP] 13 [/SUP], In-Soon Roh[SUP] 14 [/SUP], Kwang-Soo Lyoo[SUP] 15 [/SUP], Yong Jun Kim[SUP] 16 [/SUP], Seung Pil Yun[SUP] 17 [/SUP]
Affiliations
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.
Keywords: COVID-19 sequalae; DA neuron; PD; Parkinson’s disease; SARS-CoV-2; disease modeling; dopaminergic neuron; hACE2 transgenic mouse; neuroinflammation; neurological sequelae.
. 2024 May 10:101570.
doi: 10.1016/j.xcrm.2024.101570. Online ahead of print. SARS-CoV-2 infection exacerbates the cellular pathology of Parkinson's disease in human dopaminergic neurons and a mouse model
Bina Lee[SUP] 1 [/SUP], Ha Nyeoung Choi[SUP] 2 [/SUP], Young Hyun Che[SUP] 3 [/SUP], Myungjun Ko[SUP] 4 [/SUP], Hye Min Seong[SUP] 5 [/SUP], Min Gi Jo[SUP] 6 [/SUP], Seon-Hee Kim[SUP] 1 [/SUP], Chieun Song[SUP] 5 [/SUP], Subeen Yoon[SUP] 3 [/SUP], Jiwoo Choi[SUP] 3 [/SUP], Jeong Hee Kim[SUP] 3 [/SUP], Minkyeong Kim[SUP] 7 [/SUP], Min Young Lee[SUP] 8 [/SUP], Sang Won Park[SUP] 2 [/SUP], Hye Jung Kim[SUP] 2 [/SUP], Seong Jae Kim[SUP] 5 [/SUP], Do Sik Moon[SUP] 9 [/SUP], Sun Lee[SUP] 10 [/SUP], Jae-Hoon Park[SUP] 11 [/SUP], Seung-Geun Yeo[SUP] 12 [/SUP], Richard G Everson[SUP] 4 [/SUP], Young Jin Kim[SUP] 2 [/SUP], Kyung-Wook Hong[SUP] 13 [/SUP], In-Soon Roh[SUP] 14 [/SUP], Kwang-Soo Lyoo[SUP] 15 [/SUP], Yong Jun Kim[SUP] 16 [/SUP], Seung Pil Yun[SUP] 17 [/SUP]
Affiliations
- PMID: 38749422
- DOI: 10.1016/j.xcrm.2024.101570
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.
Keywords: COVID-19 sequalae; DA neuron; PD; Parkinson’s disease; SARS-CoV-2; disease modeling; dopaminergic neuron; hACE2 transgenic mouse; neuroinflammation; neurological sequelae.