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Exploiting formyl peptide receptor 2 to promote microglial resolution: a new approach to Alzheimer's disease
Edward S Wickstead1, Murray A Irving2, Stephen J Getting3
1Department of Neuroscience, University of Arizona, Tucson, AZ, USA.
Abstract:
Alzheimer's disease and dementia are among the most significant current healthcare challenges given the rapidly growing elderly population, and the almost total lack of effective therapeutic interventions. Alzheimer's disease pathology has long been considered in terms of accumulation of amyloid beta and hyperphosphorylated tau, but the importance of neuroinflammation in driving disease has taken greater precedence over the last 15-20 years. Inflammatory activation of the primary brain immune cells, the microglia, has been implicated in Alzheimer's pathogenesis through genetic, preclinical, imaging and postmortem human studies, and strategies to regulate microglial activity may hold great promise for disease modification. Neuroinflammation is necessary for defence of the brain against pathogen invasion or damage but is normally self-limiting due to the engagement of endogenous pro-resolving circuitry that terminates inflammatory activity, a process that appears to fail in Alzheimer's disease. Here, we discuss the potential for a major regulator and promoter of resolution, the receptor FPR2, to restrain pro-inflammatory microglial activity, and propose that it may serve as a valuable target for therapeutic investigation in Alzheimer's disease.
Insights
Alzheimer's disease involves neuroinflammation, particularly microglial activation. Targeting the FPR2 receptor may offer a new therapeutic strategy to control this inflammation and modify the disease.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Alzheimer's disease (AD) and dementia are growing healthcare challenges with limited treatments.
- While amyloid beta and tau were primary focuses, neuroinflammation's role in AD pathogenesis is increasingly recognized.
- Microglial activation is implicated in AD, highlighting the need for strategies to modulate their activity.
Purpose of the Study:
- To discuss the role of neuroinflammation in Alzheimer's disease pathogenesis.
- To explore the potential of the FPR2 receptor as a therapeutic target for Alzheimer's disease.
Main Methods:
- Review of genetic, preclinical, imaging, and postmortem human studies on microglial activation in AD.
- Discussion of endogenous pro-resolving mechanisms in brain inflammation.
- Focus on the receptor FPR2 as a regulator of microglial activity.
Main Results:
- Neuroinflammation, driven by microglial activation, is a key factor in Alzheimer's disease.
- The brain's natural anti-inflammatory processes appear to fail in Alzheimer's disease.
- The FPR2 receptor shows potential in restraining pro-inflammatory microglial activity.
Conclusions:
- Modulating microglial activity presents a promising avenue for Alzheimer's disease modification.
- The FPR2 receptor is a potential therapeutic target for restraining detrimental neuroinflammation in Alzheimer's disease.
