Cited by 1,047Neuroinflammation and Neurodegeneration MechanismsNeurological Disease Mechanisms and TreatmentsInflammasome and immune disorders

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Microglial Activation and Chronic Neurodegeneration

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Lull, Melinda E., Block, Michelle L.·2010·Neurotherapeutics

DOI 10.1016/j.nurt.2010.05.014PMC PMC2951017

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Abstract

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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Voltage-Gated Proton Channel Hv1 Regulates Neuroinflammation and Dopaminergic Neurodegeneration in Parkinson’s Disease Models
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Background

Authors: Lull, M. E., & Block, M. L.
Affiliations: Virginia Commonwealth University (US)
Corresponding author: Block, Michelle L.
ORCID: Lull, Melinda E.
Block, Michelle L.
Venue: Neurotherapeutics
Publisher: Elsevier BV
Published: 2010-10
Volume: 7
Issue: 4
Pages: 354-365
ISSN: 1878-7479 (ISSN-L)
DOI: 10.1016/j.nurt.2010.05.014
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4696 d)
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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Microglial Activation and Chronic Neurodegeneration

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