Neuroinflammation and Oxidative Stress in Parkinson’s Disease, Alzheimer’s Disease, and COVID-19: Microglia–Neutrophil Interaction

Abstract

and Oxidative Stress in Parkinson’s Disease, Alzheimer’s Disease, and COVID-19: Microglia–Neutrophil Interaction Authors: Ana B. de Araújo, Francisco V. C. S. Azul, Yandra Cardoso Carneiro, Caren N. S. de Sousa, Silvânia M. M. de Vasconcelos, Francisco J. Rios, Luzia K. A. M. Leal Abnormal activation of the immune system and oxidative stress are crucial factors in neurodegenerative disorders, such as Parkinson’s disease and Alzheimer’s disease. Microglia, neutrophils, oxidative stress mediators such as reactive oxygen species (ROS), lipid peroxidation products (e.g., malondialdehyde), and nitrosative stress markers (e.g., nitrite and nitrate) play important roles in neuroinflammatory mechanisms. Microglial cells acquire a proinflammatory phenotype through interactions with endogenous or exogenous compounds, including cell debris, abnormally modified proteins (including Aβ species and alpha-synuclein), and pathogens (e.g., SARS-CoV-2). They produce many inflammatory mediators and promote the activation of adjacent brain cells and leukocyte infiltration, including polymorphonuclear neutrophils. Accumulation of neutrophils in the central nervous system (CNS) leads to the secretion of more proinflammatory mediators, such as cytokines, proteases, and oxidants, and the formation of neutrophil extracellular traps (NETs). These processes are associated with the pathological activation of microglial cells, cell death, consequent influence on neuronal functions, or even neuronal death, which is a hallmark of CNS disorders. In this review, we address the importance of inflammatory mechanisms and oxidative stress in the CNS associated with Parkinson’s disease, Alzheimer’s disease, and the neuronal effects observed in coronavirus disease 2019 (COVID-19), as observed by the abnormal activation of central and peripheral immune cells, such as microglia and neutrophils. We also discuss emerging evidence linking SARS-CoV-2 infection to neuroinflammatory mechanisms that could contribute to neurodegenerative complications.