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, 16 (5), 508-518

Microglia and Astrocytes in Alzheimer's Disease: Implications for Therapy


Microglia and Astrocytes in Alzheimer's Disease: Implications for Therapy

Marc Fakhoury. Curr Neuropharmacol.


Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the progressive loss of neurons, which typically leads to severe impairments in cognitive functions including memory and learning. Key pathological features of this disease include the deposition of highly insoluble amyloid β peptides and the formation of neurofibrillary tangles (NFTs) in the brain. Mounting evidence also implicates sustained glial-mediated inflammation as a major contributor of the neurodegenerative processes and cognitive deficits observed in AD.

Methods: This paper provides an overview of findings from both human and animal studies investigating the role of microglia and astrocytes in AD, and discusses potential avenues for therapeutic intervention.

Results: Glial-mediated inflammation is a 'double-edged sword', performing both detrimental and beneficial functions in AD. Despite tremendous effort in elucidating the molecular and cellular mechanisms underlying AD pathology, to date, there is no treatment that could prevent or cure this disease. Current treatments are only useful in slowing down the progression of AD and helping patients manage some of their behavioral and cognitive symptoms.

Conclusion: A better understanding of the role of microglia and astrocytes in the regulation of AD pathology is needed as this could pave the way for new therapeutic strategies.

Keywords: Alzheimer's disease; astrocytes; cytokines; glial cells; inflammation; microglia..


Fig. (1)
Fig. (1)
Detrimental effects of glial-mediated inflammation. Activation of microglia and astrocytes by Aβ or following a signal of damage leads to the secretion and release of inflammatory chemokines and cytokines, including IL-1, IL-6, and TNF-α. These pro-inflammatory elements trigger a cascade of events, such as oxidative stress, demyelination and apoptosis, which eventually lead to neurodegeneration and cognitive decline. Reactive astrocytes also contribute to scar formation around injured tissue by accumulating around amyloid plaques. Adapted with permission from [65]. (The color version of the figure is available in the electronic copy of the article).
Fig. (2)
Fig. (2)
Differential effects of NSAIDs on microglia and AD pathogenesis. The therapeutic effects of NSAIDs may differ depending on the stage of AD. Alternatively activated (M2) microglia are present during the early stage of the disease, whereas classically activated (M1) microglia are present during the late stage of the disease. Furthermore, different subsets of NSAIDs have different affinity for immune and inflammatory targets in the brain, thus resulting in a range of effects including reduced inflammatory mediators and altered Aβ production. Abbreviations: insulin degrading enzyme (IDE); scavenger receptors (SC). Adapted with permission from [120].

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