Targeting innate immunity for neurodegenerative disorders of the central nervous system

J Neurochem, 2016 · DOI: 10.1111/jnc.13667 · Published: September 1, 2016

Simple Explanation

Neuroinflammation is a critical factor in many neurodegenerative diseases. Therefore, intervening in the signaling pathways that activate the innate immune system could be a useful way to treat these diseases. This article reviews updates on innate immunity in acute brain injury and chronic neurodegenerative disorders. It also discusses the roles of astrocytes and microglia, and presents new technical tools that may help us understand neuroinflammatory mechanisms. The review covers topics such as microglial ontogeny, TREM2 signaling, and the cytokine paradox in Alzheimer’s disease.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review and meeting report

Key Findings

1
Microglia, the brain's immune cells, have diverse morphologies and functions depending on their environment and stage of development.
2
Understanding microglial ontogeny and using induced pluripotent stem cells can help generate microglia-like cells for therapeutic use and study.
3
In Alzheimer’s disease, the role of cytokines is complex. Some cytokines can be beneficial by reducing amyloid deposits, while others can be detrimental by exacerbating tau phosphorylation.

Research Summary

Neuroinflammation plays a critical role in neurodegenerative diseases, making innate immune activation a promising therapeutic target. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7-9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer’s disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. The series covers microglial morphology, PGE2 receptors, arginine metabolism, technical challenges in microglia and astrocyte cultures, microglial ontogeny, TREM2 signaling, and the cytokine paradox in Alzheimer’s disease.

Practical Implications

Therapeutic Targets

Signaling steps of innate immune activation represent promising therapeutic targets for neurodegenerative disorders.

Microglial Modulation

Modulation of microglial responses is an attractive therapeutic target, requiring a thorough understanding of their origin and development.

Rebalancing Inflammation

Rebalancing neuroinflammation toward a beneficial, homeostatic innate immune response may harness innate immunity against Alzheimer’s disease.

Study Limitations

1
The artificial nature of cell culture systems may not fully represent in vivo conditions.
2
Heterogeneity in microglia and their responses makes it difficult to determine which responses are beneficial and which are harmful.
3
Limited clinical literature on persistent inflammation after traumatic brain injury makes it difficult to assess long-term impacts on dementia risk.

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