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Microglial Activation and Chronic Neurodegeneration
Open accessAbstract
Microglia, the resident innate immune cells in the brain, have long been implicated in the pathology of neurodegenerative diseases. Accumulating evidence points to activated microglia as a chronic source of multiple neurotoxic factors, including tumor necrosis factor-α, nitric oxide, interleukin-1β, and reactive oxygen species (ROS), driving progressive neuron damage. Microglia can become chronically activated by either a single stimulus (e.g., lipopolysaccharide or neuron damage) or multiple stimuli exposures to result in cumulative neuronal loss with time. Although the mechanisms driving these phenomena are just beginning to be understood, reactive microgliosis (the microglial response to neuron damage) and ROS have been implicated as key mechanisms of chronic and neurotoxic microglial activation, particularly in the case of Parkinson's disease. We review the mechanisms of neurotoxicity associated with chronic microglial activation and discuss the role of neuronal death and microglial ROS driving the chronic and toxic microglial phenotype.
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“MiRNAs can ameliorate degeneration by suppressing microglial activation in the brain and are therefore considered as a therapeutic approach for neurodegenerative diseases (Lull and Block 2010).”
From MiR-124 and MiR-155 as Therapeutic Targets in Microglia-Mediated Inflammation in Multiple Sclerosis (2025) · cites this paper as Lull and Block 2010
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“The notion that neuroinflammatory processes contribute to disease was once provocative, yet recent studies have uncovered multiple mechanisms by which aberrant gliosis causes detrimental neuroinflammation that can influence tau pathology and accelerate neurodegeneration.”
From Glial contributions to neurodegeneration in tauopathies (2017) · cites this paper as [6]
In the citing paper
“After this acute M1 activation, microglial cells can suffer an uncontrolled activation leading to a state of chronic inflammation. In this state, microglia release neurotoxic inflammatory factors (TNF-α, IL-1α, IL-1β, IL-6, NO, hydrogen peroxide, superoxide anion, chemokines, and glutamate), which lead to neuronal death (Block et al., 2007; Lull and Block, 2010; Burguillos et al., 2011; Kettenmann”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Lull and Block, 2010
In the citing paper
“Neuroinflammation is a characteristic of neurodegenerative diseases, including PD, in which microglia confer pathogenic and exacerbating effects (Lull and Block, 2010; Zhao et al., 2020).”
From Mechanism of miR-132-3p Promoting Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson’s Disease (2022) · cites this paper as Lull and Block, 2010
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“In vivo studies also emphasize the important role of inflammation as a toxic component of MPTP/MPP neurotoxicity,(161) in which DA neuron damage in response to MPTP is significantly reduced in mutant mice with deficient production of pro-inflammatory factors, such as nitric oxide,(162) superoxide,(137,163) prostagland…”
BackgroundCritical Role for Microglial NADPH Oxidase in Rotenone-Induced Degeneration of Dopaminergic Neurons
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“Recently, we used an in vitro approach to separate neuron injury factors from the cellular actors of reactive microgliosis in an attempt to begin to discover molecular signals (soluble neuron injury factors) responsible for chronic and toxic microglial activation.166 We found that when injury with the DA neurotoxin MP…”
BackgroundInfluentialSelf-citationEvidence for synaptic stripping by cortical microglia
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BackgroundInfluentialThe influence of microglia on the pathogenesis of Parkinson's disease
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“Recently, we used an in vitro approach to separate neuron injury factors from the cellular actors of reactive microgliosis in an attempt to begin to discover molecular signals (soluble neuron injury factors) responsible for chronic and toxic microglial activation.166 We found that when injury with the DA neurotoxin MP…”
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“in vitro causing the progressive and cumulative loss of DA neurons with time.(129,169,170) Although traditionally”
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“In addition, microglia have also been shown to release anti-inflammatory and trophic molecules to enhance the survival of surrounding neurons.(43,44) Thus, evidence supports that when microglia become neurotoxic, this is due to both the loss of the beneficial functions(36) and/or a shift to a pro-inflammatory phenotyp…”
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“tially ramified microglia followed by the development of fully ramified, or branched, microglia that express cell surface molecules characteristic of resting microglia (discussed as follows).(7) Although the origin of initial microglia populations within the CNS has been well supported, the replacement of microglial p…”
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“in vitro causing the progressive and cumulative loss of DA neurons with time.(129,169,170) Although traditionally”
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“In addition to increases in microglia-released ROS and proinflammatory cytokines, microglia may play a large part in the initiation of disease by acting as antigenpresenting cells targeting myelin.(87) In HIV-associated neurocognitive disorder, microglia play a strong part in harboring the HIV and acting as a site of…”
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“Interestingly, LPS has been implicated in the potential etiology of sporadic PD through sepsis and early life exposure during pregnancy.(169,172,173) Furthermore, diagnosed symptoms of PD, brain inflammation, and damage to the SN have been described in a patient who had received accidental systemic administration of L…”
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“In fact, recent work has indicated that the MAC-1 receptor is responsible for the LPS-induced activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the consequent production of O2 ● in microglia.(49) Thus, the microglial (O2 ● ) response is typical (although less robust) when compared with othe…”
BackgroundGangliosides activate microglia via protein kinase C and NADPH oxidase
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Degenerating Synaptic Boutons in Prion Disease
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“Specifically in response to injury, activated microglia have been shown to surround damaged neurons and participate in synaptic stripping, a process of removing branches from damaged neurons to promote repair and regrowth,(35,40,41) although recent evidence shows that microglia may play an indirect, anti-inflammatory…”
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“In addition, microglia have also been shown to release anti-inflammatory and trophic molecules to enhance the survival of surrounding neurons.(43,44) Thus, evidence supports that when microglia become neurotoxic, this is due to both the loss of the beneficial functions(36) and/or a shift to a pro-inflammatory phenotyp…”
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“These myeloid cells can be found within the CNS by embryonic day 8 in rodents,(4) and by week 12 of gestation in humans.(5) At this stage, the cells are referred”
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“In HIV-associated neurocognitive disorder, microglia play a strong part in harboring the HIV and acting as a site of viral replication.(88,89) During this process, microglia become activated and release pro-inflammatory cytokines.”
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“microglia are also present in the brains ofMPTP intoxicated monkeys.(119,120) Using positron emission tomographic im-”
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Vpr- and Nef-Dependent Induction of RANTES/CCL5 in Microglial Cells
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“Reactive microgliosis-chronic response to a single stimulus Although microglial activation was initially perceived as a transient event,(31) it is now believed to be chronic and culpable in the propagation of disease.(1,94,157) Reports have shown that microglia can remain chronically activated(140,158,159) in a proces…”
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“plicated in several cellular functions, such as migration(134) and phagocytosis.(135) Specific to microglia, ROS”
BackgroundMicroglial NADPH Oxidase Mediates Leucine Enkephalin Dopaminergic Neuroprotection
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Amyloid and Alzheimer's disease—Cause or effect?
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Flagged first, then by citations
1 of the 182 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
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“However, inflammation in tissue pathology that may result in the production of neurotoxic factors amplifying the disease states, indicates the persistence of inflammatory stimuli or failure in normal resolution mechanisms (16,17).”
Paracrine Mechanisms of Mesenchymal Stem Cell-Based Therapy: Current Status and Perspectives
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Neuroinflammation as a common feature of neurodegenerative disorders
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“OS is thought to be the underlying etiology that leads to cellular dysfunction and demise in both idiopathic and genetic cases of PD (Hwang, 2013; Lull and Block, 2010).”
Background
Metadata
- Authors
- Lull, M. E., & Block, M. L.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- Block, Michelle L.
- Venue
- Neurotherapeutics
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 7
- Issue
- 4
- Pages
- 354-365
- ISSN
- 1878-7479 (ISSN-L)
- PMC
- PMC2951017
- OpenAlex
- W2050320551
- Cited by
- 1,047
- References
- 182
- Citations by year
- 2026: 50 · 2025: 112 · 2024: 94 · 2023: 60 · 2022: 84 · 2021: 95 · 2020: 84 · 2019: 78 · 2018: 83 · 2017: 76 · 2016: 73 · 2015: 43 · 2014: 38 · 2013: 28 · 2012: 30
- FWCI
- 14.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neurotherapeutics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Fisher Digital Publications (St. John Fisher College) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Environmental Health Sciences (R01ES016951, R00ES01549)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- microglial activation, neurodegeneration, reactive microgliosis, reactive oxygen species, neuroinflammation, neurotoxicity, Parkinson's disease, neuronal cell death, lipopolysaccharide, TNF-α, nitric oxide, IL-1β
- MeSH terms
- Animals, Chronic Disease, Dopamine, Humans, Models, Biological, Neurons, Oxidation-Reduction, Signal Transduction, Reactive Oxygen Species, Microglia, NADPH Oxidases, Neurodegenerative Diseases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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