COVID-19 and Parkinson’s disease: shared inflammatory pathways under oxidative stress

Abstract

The current coronavirus pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a serious global health crisis. It is a major concern for individuals living with chronic disorders such as Parkinson’s disease (PD). Increasing evidence suggests an involvement of oxidative stress and contribution of NFκB in the development of both COVID-19 and PD. Though, it is early to identify if SARS-CoV-2 led infection enhances PD complications, it is likely that oxidative stress may exacerbate PD progression in COVID-19 affected individuals and/or vice versa. In the current study, we sought to investigate whether NFκB-associated inflammatory pathways following oxidative stress in SARS-CoV-2 and PD patients are correlated. Toward this goal, we have integrated bioinformatics analysis obtained from BLASTP search for similarities between SARS-CoV-2 proteins and human proteome, literature review, and laboratory data obtained in a human cell model of PD. A Parkinson’s like state was created in 6OHDA-induced differentiated dopaminergic neurons (dDCNs) obtained from ReNVM cell line. The results indicated that SARS-CoV-2 infection and 6OHDA-induced toxicity triggered stimulation of caspases -2, -3 and -8 via the NFκB pathway resulting in death of dDCNs. Furthermore, specific inhibitors for NFκB and studied caspases reduced the death of stressed dDCNs. The findings suggest that knowledge of the selective inhibition of caspases and NFκB activation may contribute to development of potential therapeutic approaches for the treatment of COVID-19 and PD.