The DOI matches its Crossref record; 181 of the 182 references it cites were found in a registry or an index.
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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Citations
Cites
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1 of the 182 references couldn’t be matched to a known paper.
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l -Carnitine Inhibits Lipopolysaccharide-Induced Nitric Oxide Production of SIM-A9 Microglia Cells
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“The pathophysiology of viral infections is complex and already in the 1990s there were findings showing that reactive oxygen species (ROS) and reactive nitrogen species (RNS) play certain role in these infections [8], although the relevance of oxidative stress in development of viral diseases has not been well explore…”
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“However, the chronically activated microglia that are commonly observed in neurodegeneration seem to significantly differ from senescent microglia in semantics only (Lull and Block, 2010; Woodburn et al., 2021).”
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“Discussion Activated microglia play an important role in the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease [16, 17].”
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“While they provide these important functions to regulate brain health, microglia can also become dysregulated with sustained activation [21,22] and contribute to neuropathology [23,24].”
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“****p 0.0001, **p 0.01, *p 0.05, ns = not significant, two‑way ANOVA followed by Tukey’s multiple comparisons test increase in the expression of MHC II in microglia by gossypetin suggest more than what we currently understand about microglia and immune system in CNS.”
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Kim, M.-Y., & Pang, E. (2025) · Ewha Medical Journal · doi:10.12771/emj.2025.00101 · Cited by 41
“This process triggers microglial activation and the release of pro-inflammatory cytokines, such as TNF-α and IL-1β, which further contribute to neuronal damage [137,138].”
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Dihydromyricetin attenuates inflammation through TLR4/NF-kappaB pathway
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“Over-activation of microglia releases pro-inflammatory cytokines including IL-6, IL‐1β and TNF-α, which would lead to the damage of neurons and further active the inflammatory cascade [12].”
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Slowing Alzheimer’s disease progression through probiotic supplementation
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“Microglia-mediated neuroinflammation featured by the production of cytotoxic factors released from activated microglia has been shown to damage dopamine neurons in the substantia nigra pars compacta (Lull & Block, 2010; Ouchi et al., 2005).”
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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
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