Let's make microglia great again in neurodegenerative disorders

Area of Science:

• Neuroimmunology
• Neurodegenerative Diseases
• Innate Immunity

Background:

• Common neurodegenerative disorders like Alzheimer's, Parkinson's, ALS, and prion diseases share a hallmark: the accumulation of misfolded proteins.
• This protein aggregation triggers chronic neuroinflammation, characterized by activated microglia and the release of inflammatory cytokines and chemokines.
• A critical early defect in these diseases is impaired microglial phagocytosis, hindering the clearance of toxic misfolded proteins.

Purpose of the Study:

• To identify common immune pathologies across major neurodegenerative disorders.
• To explore the potential of targeting aberrant innate immune pathways for therapeutic benefit.
• To investigate strategies for restoring microglial function to enhance the clearance of neurotoxic proteins.

Main Methods:

• This is a review article, synthesizing existing research on neuroinflammation and proteinopathies in neurodegenerative diseases.
• Analysis of shared immune mechanisms and microglial dysfunction across different neurodegenerative conditions.
• Exploration of innate immune pathways as potential therapeutic targets.

Main Results:

• Identified shared immune pathologies, particularly concerning microglia activation and dysfunction, in major neurodegenerative disorders.
• Highlighted the compromised phagocytic capacity of microglia as a common early event.
• Emphasized the role of chronic neuroinflammation driven by aberrant innate immune responses.

Conclusions:

• Aberrant innate immune pathways are a common feature of major neurodegenerative diseases.
• Restoring immune homeostasis by targeting these pathways offers a potential therapeutic strategy.
• Coaxing microglia to effectively clear neurotoxic misfolded proteins is a key goal for future treatments.