NIH Study Implicates Hyperactive Immune System in Aging Brain Disorders

  

Understanding Aging Brain Disorders. In a study of flies, NIH scientists showed how the immune system may be a culprit in the damage caused by aging brain disorders. 

Courtesy of Giniger lab, NIH/NINDS.

In this study, published in Cell Reports, they suggested that altering Cdk5 resulted in the death of dopamine releasing neurons, especially in the brains of older flies. Typically, Parkinson’s disease damages the same types of cells in humans. Further experiments in flies suggested the neuron loss happened because altering Cdk5 slowed autophagy, or a cell’s waste disposal system that rids the body of damaged cells in a contained, controlled fashion, which in turn triggered the immune system to attack the animal’s own neurons. 

This immune system attack is a much “messier” and more diffuse process than autophagy. Genetically restoring the waste system or blocking the immune system’s responses prevented the reduction in dopamine neurons caused by altering Cdk5. The authors concluded that this chain reaction in which a breakdown in autophagy triggers a widely destructive immune reaction may occur in human brain during several neurodegenerative disorders and that researchers may want to look to these systems for new treatment targets and strategies.

 This study was supported by the Intramural Research Program at the NINDS (NS003106).

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Citation: Shukla et al. Hyperactive innate immunity causes degeneration of dopamine neurons upon altering activity of Cdk5, January 2, 2019, Cell Reports