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

TL;DR

This paper reviews how immune system activation and oxidative stress contribute to brain diseases like Parkinson’s, Alzheimer’s, and complications from COVID-19.

Contribution

It highlights the novel role of microglia–neutrophil interactions in driving neuroinflammation and oxidative stress across multiple neurological conditions.

Findings

Microglia and neutrophils interact to promote neuroinflammation through the release of reactive oxygen species and cytokines.

Neutrophil extracellular traps and oxidative stress markers are linked to neuronal damage in Parkinson’s and Alzheimer’s.

SARS-CoV-2 infection may trigger neuroinflammatory pathways that resemble those in neurodegenerative diseases.

Abstract

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.

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