2018
DOI: 10.1111/bph.14546
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The involvement of microglia in Alzheimer's disease: a new dog in the fight

Abstract: First described clinically in 1906, Alzheimer's disease (AD) is the most common neurodegenerative disease and form of dementia worldwide. Despite its prevalence, only five therapies are currently approved for AD, all dealing with the symptoms rather than the underlying causes of the disease. A multitude of experimental evidence has suggested that the once thought inconsequential process of neuroinflammation does, in fact, contribute to the AD pathogenesis. One such CNS cell type critical to this process are mi… Show more

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Cited by 24 publications
(14 citation statements)
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“…As previously discussed, rather than focusing on neurons as a pharmacological target, microglia could serve as a more upstream cellular target of interest in PD since microglia are involved in αSYN trafficking, aggregation, and clearance, and are closely associated with the triggers for the neuroinflammation process (Ferreira and Romero-Ramos, 2018;Moore et al, 2018;Xia et al, 2019). Further investigation into how antioxidantbased composite NPs may influence αSYN transmission among microglia and other CNS cells, especially neurons, would provide valuable insight into the interplay between different CNS cell types in the trafficking and aggregation of αSYN and its related pathology.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…As previously discussed, rather than focusing on neurons as a pharmacological target, microglia could serve as a more upstream cellular target of interest in PD since microglia are involved in αSYN trafficking, aggregation, and clearance, and are closely associated with the triggers for the neuroinflammation process (Ferreira and Romero-Ramos, 2018;Moore et al, 2018;Xia et al, 2019). Further investigation into how antioxidantbased composite NPs may influence αSYN transmission among microglia and other CNS cells, especially neurons, would provide valuable insight into the interplay between different CNS cell types in the trafficking and aggregation of αSYN and its related pathology.…”
Section: Discussionmentioning
confidence: 99%
“…Microglial activation is one of the main neuroinflammatory mechanisms that contributes to neuronal degeneration, as shown by post-mortem and in vivo studies in PD (Hirsch and Hunot, 2009;Moore et al, 2018). Release of pro-inflammatory cytokines and reactive free radicals such as tumor necrosis factor (TNFα), interleukin-6 (IL-6) nitric oxide (NO), reactive oxygen species (ROS) and extracellular vesicles containing toxic protein aggregates resulting from microglial activation can lead to the degeneration and death of neighboring healthy neurons, particularly DA neurons (Hoenen et al, 2016;Subramaniam and Federoff, 2017).…”
Section: Introductionmentioning
confidence: 99%
“…Astrocyte dysfunction has been shown to result in an increase of pro-inflammatory mediators release, decrease of glutamate uptake, loss of synapses, and ultimately cognitive deficits in AD ( 124 ). A number of recent reviews further examine particular aspects of the role of microglia and astrocytes in the neuroinflammatory response in AD, including phenotypical and functional changes, genetic variants of the innate microglial immune receptor TREM2, which has been associated with an increased risk of LOAD ( 105 , 125 129 ).…”
Section: Neuroinflammation: At the Center Of The Infectious Hypothesimentioning
confidence: 99%
“…Damage of synapses is the most important step for brain dysfunction (Morrison and Baxter, 2012), and the degree of synaptic changes correlates with the severity of cognitive decline (Sheng et al, 2012). Synaptic dysfunction and neurotoxicity in age-associated dementia and AD are mainly caused by amyloid plaques, but also neuroinflammation with reactive microglia (Moore et al, 2019). Mitochondria are also involved in synaptic degeneration due to compromised ATP synthesis (energy failure), as well as impaired Ca 2+ handling, increased production of reactive oxygen species (ROS), impaired production of metabolites that are neurotransmitter precursors, and dysregulation of mitochondrial dynamics and mitochondriadependent cell signaling transduction (Tait and Green, 2012;Guo et al, 2017;Belenguer et al, 2019).…”
Section: Synaptic Dysfunctionmentioning
confidence: 99%