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Published on: October 25, 2016
Microglia as a cellular target of diclofenac therapy in Alzheimer's disease
Barbara E Stopschinski1,2, Rick A Weideman3, Danni McMahan3
1Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Abstract:
Alzheimer's disease (AD) is an untreatable cause of dementia, and new therapeutic approaches are urgently needed. AD pathology is defined by extracellular amyloid plaques and intracellular neurofibrillary tangles. Research of the past decades has suggested that neuroinflammation plays a critical role in the pathophysiology of AD. This has led to the idea that anti-inflammatory treatments might be beneficial. Early studies investigated non-steroidal anti-inflammatory drugs (NSAIDS) such as indomethacin, celecoxib, ibuprofen, and naproxen, which had no benefit. More recently, protective effects of diclofenac and NSAIDs in the fenamate group have been reported. Diclofenac decreased the frequency of AD significantly compared to other NSAIDs in a large retrospective cohort study. Diclofenac and fenamates share similar chemical structures, and evidence from cell and mouse models suggests that they inhibit the release of pro-inflammatory mediators from microglia with leads to the reduction of AD pathology. Here, we review the potential role of diclofenac and NSAIDs in the fenamate group for targeting AD pathology with a focus on its potential effects on microglia.
Insights
Diclofenac and fenamate NSAIDs show promise in reducing Alzheimer's disease (AD) pathology by targeting neuroinflammation. These drugs may inhibit microglial pro-inflammatory mediators, offering a potential new therapeutic avenue for AD.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Alzheimer's disease (AD) is a leading cause of dementia with no effective treatments.
- Neuroinflammation is increasingly recognized as a key factor in AD pathogenesis.
- Previous studies on NSAIDs for AD yielded mixed results.
Purpose of the Study:
- To review the potential of diclofenac and fenamate NSAIDs in targeting AD pathology.
- To explore the effects of these drugs on microglia and neuroinflammation.
- To assess their therapeutic potential for Alzheimer's disease.
Main Methods:
- Review of existing literature on diclofenac, fenamates, and their role in AD.
- Analysis of evidence from cell and mouse models regarding anti-inflammatory mechanisms.
- Examination of retrospective cohort studies comparing NSAID efficacy in AD.
Main Results:
- Diclofenac demonstrated a significant decrease in AD frequency compared to other NSAIDs in a large cohort study.
- Diclofenac and fenamates share structural similarities and may inhibit pro-inflammatory mediator release from microglia.
- Evidence suggests these drugs can reduce AD pathology by modulating microglial activity.
Conclusions:
- Diclofenac and fenamate NSAIDs represent a promising therapeutic strategy for Alzheimer's disease.
- Targeting microglial-mediated neuroinflammation with these agents may reduce AD pathology.
- Further research into diclofenac and fenamates could lead to novel treatments for AD.
