| Abstrakt: |
The pathophysiology of Parkinson's disease (PD) is marked by degeneration of dopaminergic neurons in the substantia nigra. With advent of COVID-19, which is closely associated with generalized inflammation and multiple organ dysfunctions, the PD patients may develop severe conditions of disease leading to exacerbated degeneration. This condition is caused by the excessive release of pro-inflammatory markers, called cytokine storm, that is capable of triggering neurodegenerative conditions by affecting the blood–brain barrier (BBB). A possible SARS-CoV-2 infection, in serious cases, may compromise the immune system by triggering a hyperstimulation of the neuroimmune response, similar to the pathological processes found in PD. From this perspective, the inflammatory scenario triggers oxidative stress and, consequently, cellular dysfunction in the nervous tissue. The P2X7R seems to be the key mediator of the neuroinflammatory process, as it acts by increasing the concentration of ATP, allowing the influx of Ca2+ and the occurrence of mutations in the α-synuclein protein, causing activation of this receptor. Thus, modulation of the purinergic system may have therapeutic potential on the effects of PD, as well as on the damage caused by inflammation of the BBB, which may be able to mitigate the neurodegeneration caused by diseases. Considering all the processes of neuroinflammation, oxidative stress, and mitochondrial dysfunction that PD propose, we can conclude that the P2X7 antagonist acts in the prevention of viral diseases, and it also controls purinergic receptors formed by multi-target compounds directed to self-amplification circuits and, therefore, may be a viable strategy to obtain the desired disease-modifying effect. Thus, purinergic system receptor modulations have a high therapeutic potential for neurodegenerative diseases such as PD. Highlights: Parkinson's disease (PD) is a neurodegeneration of public health importance. The pathophysiology of PD is associated with oxidative stress and mitochondrial dysfunction. COVID-19 increase lethality by the exacerbation of neurodegeneration. Purinergic signaling participates of immune response, neuroinflammation, and oxidative stress processes. Inhibition of P2X7R reduces exacerbated inflammation and oxidative stress triggered by microglia activity. P2Y6R is highly expressed in individuals with PD and may serve as a biomarker for the disease. Receptors such as P2Y6, P2X4, and P2Y12 are closely associated with neuroinflammation and neuronal dysfunctions. Impaired P2X1 activity enables the accumulation of α-synuclein in neurons. [ABSTRACT FROM AUTHOR] |
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