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  • COVID-19 and Parkinson's Disease: Shared Inflammatory Pathways Under Oxidative Stress.

COVID-19 and Parkinson's Disease: Shared Inflammatory Pathways Under Oxidative Stress.

Brain sciences (2020-11-05)
Zahara L Chaudhry, Donika Klenja, Najma Janjua, Gerta Cami-Kobeci, Bushra Y Ahmed
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. Although, 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 Basic Local Alignment Search Tool of Protein Database (BLASTP) search for similarities of SARS-CoV-2 proteins against human proteome, literature review, and laboratory data obtained in a human cell model of PD. A Parkinson's like state was created in 6-hydroxydopamine (6OHDA)-induced differentiated dopamine-containing neurons (dDCNs) obtained from an immortalized human neural progenitor cell line derived from the ventral mesencephalon region of the brain (ReNVM). 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 the 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 the development of potential therapeutic approaches for the treatment of COVID-19 and PD.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Caspase 3 Antibody, active (cleaved) form, Chemicon®, from rabbit
Sigma-Aldrich
Caspase-8 Inhibitor II, The Caspase-8 Inhibitor II controls the biological activity of Caspase-8. This small molecule/inhibitor is primarily used for Cancer applications.
Sigma-Aldrich
IKK-2 Inhibitor, SC-514, The IKK-2 Inhibitor, SC-514, also referenced under CAS 354812-17-2, controls the biological activity of IKK-2. This small molecule/inhibitor is primarily used for Inflammation/Immunology applications.
Sigma-Aldrich
Anti-NFκB Antibody, p65 subunit, active subunit, clone 12H11, clone 12H11, Chemicon®, from mouse
Sigma-Aldrich
Caspase-2 Inhibitor I, The Caspase-2 Inhibitor I controls the biological activity of Caspase-2. This small molecule/inhibitor is primarily used for Cancer applications.