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. 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 Sequence 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.

Emerging COVID-19 Neurological Manifestations: Present Outlook and Potential Neurological Challenges in COVID-19 Pandemic

“…Recently, Chaudhry et al reported that SARS-CoV-2 infection in 6-hydroxydopamine-treated dopamine-containing neurons caused activation of caspase cascade via NF-κB signaling resulting in the death of dopaminergic neurons [32]. Activation of NF-κB signaling could impart neurodegenerative effects through pro-apoptotic and proinflammatory mechanisms (Fig.…”

Common Inflammatory Mechanisms in COVID-19 and Parkinson’s Diseases: The Role of Microbiome, Pharmabiotics and Postbiotics in Their Prevention

“…It is reported that COVID-19 enters the cell by interacting with the angiotensin-converting enzyme II receptor ACE2 and transmembrane serine protease-2 TMPRSS2. [1][2][3] Therefore, serum angiotensin 2 AngII levels increase as a result of its reduced degradation by ACE2. Accumulated AngII has been shown to activate inflammatory cytokines, including interferon-gamma, followed by interferon gene stimulation, resulting in increased cytokine storm and associated acute respiratory distress syndrome, as seen in severe disease.…”

“…Accumulated AngII has been shown to activate inflammatory cytokines, including interferon-gamma, followed by interferon gene stimulation, resulting in increased cytokine storm and associated acute respiratory distress syndrome, as seen in severe disease. 1,[4][5][6] Moreover, activation of cytokines leads to hyperactivation of downstream signaling cascades, including nuclear transcription factor kappa B NF-κB, which is usually activated by SARS-CoV-2 itself via pattern recognition receptors. 1,5,7 Elevated levels of reactive oxygen species by SARS-CoV -2 can cause redox imbalances, increase the amount of lipid peroxidation products, and open the transition pores of mitochondrial permeability.…”

Parkinson’s Disease and the COVID-19 Pandemic

“…Pro-inflammatory cytokines (TNF and IL-1 β ) have been associated with increased PD risk, while use anti-TNF biologics may reduce the risk [ 84 ]. Finally, oxidative stress and NF- κ B have also been suspected to play a role in the development of both COVID-19 and PD [ 81 ].…”