Changing paradigm to target microglia in neurodegenerative diseases: from anti-inflammatory strategy to active
Emiliano Peña-Altamira1, Federica Prati1, Francesca Massenzio1
1a Department of Pharmacy and Biotechnology , University of Bologna , Bologna , Italy.
Introduction:
The importance of microglia in most neurodegenerative pathologies, from Parkinson's disease to amyotrophic lateral sclerosis and Alzheimer's disease, is increasingly recognized. Until few years ago, microglial activation in pathological conditions was considered dangerous to neurons due to its causing inflammation. Today we know that these glial cells also play a crucial physiological and neuroprotective role, which is altered in neurodegenerative conditions.
Areas Covered:
The neuroinflammatory hypothesis for neurodegenerative diseases has led to the trial of anti-inflammatory agents as therapeutics with largely disappointing results. New information about the physiopathological role of microglia has highlighted the importance of immunomodulation as a potential new therapeutic approach. This review summarizes knowledge on microglia as a potential therapeutic target in the most common neurodegenerative diseases, with focus on compounds directed toward the modulation of microglial immune response through specific molecular pathways.
Expert Opinion:
Here we support the innovative concept of targeting microglial cells by modulating their activity, rather than simply trying to counteract their inflammatory neurotoxicity, as a potential therapeutic approach for neurodegenerative diseases. The advantage of this therapeutic approach could be to reduce neuroinflammation and toxicity, while at the same time strengthening intrinsic neuroprotective properties of microglia and promoting neuroregeneration.
Insights
Targeting microglia, the brain's immune cells, offers a new therapeutic strategy for neurodegenerative diseases. Modulating their function can reduce inflammation and enhance neuroprotection, promoting brain repair.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglia are increasingly recognized for their critical role in neurodegenerative diseases like Alzheimer's, Parkinson's, and ALS.
- Once viewed solely as inflammatory agents detrimental to neurons, microglia are now understood to possess vital neuroprotective functions.
- These crucial physiological roles are often dysregulated in the context of neurodegeneration.
Purpose of the Study:
- To review microglia as a therapeutic target for common neurodegenerative diseases.
- To explore compounds that modulate microglial immune responses via specific molecular pathways.
- To highlight immunomodulation as a promising therapeutic strategy.
Main Methods:
- Review of current literature on microglial function in neurodegeneration.
- Analysis of therapeutic approaches targeting microglial immune pathways.
- Focus on compounds modulating specific molecular pathways of microglial response.
Main Results:
- Anti-inflammatory agents have shown limited success in treating neurodegenerative diseases.
- Targeting microglial immunomodulation presents a novel therapeutic avenue.
- Specific molecular pathways offer opportunities for targeted intervention.
Conclusions:
- Modulating microglial activity, rather than solely counteracting inflammation, is a promising therapeutic concept.
- This approach aims to reduce neuroinflammation and toxicity.
- It also seeks to enhance microglia's intrinsic neuroprotective properties and promote neuroregeneration.
