Related Mechanisms: [Neuroinflammation](/mechanisms/neuroinflammation), [Microglial Activation](/mechanisms/microglial-phagocytosis), [Blood-Brain Barrier Breakdown](/mechanisms/blood-brain-barrier-breakdown)
Overview
NETosis is a specialized form of cell death in neutrophils that results in the release of neutrophil extracellular traps (NETs) — webs of chromatin fibers decorated with antimicrobial proteins including neutrophil elastase (NE), myeloperoxidase (MPO), and histones[@brinkmann2004]. Originally described as a defense mechanism against pathogens, dysregulated NETosis has been increasingly implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD)[@caielli2022].
Molecular Mechanism
Classical NETosis Pathway
Neutrophil activation triggers a cascade of events leading to NET release:
Neutrophil activation — via receptors (TLRs, complement receptors, Fcγ receptors) or pathogens
NET release — chromatin and associated proteins expelled extracellularly[@papayannopoulos2017]
NETosis Pathway in Neurodegeneration
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NETosis in Neurodegeneration
Related Mechanisms: [Neuroinflammation](/mechanisms/neuroinflammation), [Microglial Activation](/mechanisms/microglial-phagocytosis), [Blood-Brain Barrier Breakdown](/mechanisms/blood-brain-barrier-breakdown)
Overview
NETosis is a specialized form of cell death in neutrophils that results in the release of neutrophil extracellular traps (NETs) — webs of chromatin fibers decorated with antimicrobial proteins including neutrophil elastase (NE), myeloperoxidase (MPO), and histones[@brinkmann2004]. Originally described as a defense mechanism against pathogens, dysregulated NETosis has been increasingly implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD)[@caielli2022].
Molecular Mechanism
Classical NETosis Pathway
Neutrophil activation triggers a cascade of events leading to NET release:
Neutrophil activation — via receptors (TLRs, complement receptors, Fcγ receptors) or pathogens
NET release — chromatin and associated proteins expelled extracellularly[@papayannopoulos2017]
NETosis Pathway in Neurodegeneration
Mermaid diagram (expand to render)
Vital NETosis
An alternative, non-lytic pathway where NETs are released from viable neutrophils, involving nuclear envelope budding and nuclear-derived vesicles[@yousefi2020].