Reduced autophagy efficiency induces innate immune activation leading to neurodegeneration

Abstract

Macroautophagy/autophagy and innate immunity are central processes in neurodegeneration, but it has been unclear whether they work independently or in combination to assault the neuron. We recently demonstrated that reduced efficiency of autophagy causes hyperactivation of innate immunity, which in turn is necessary and sufficient for loss of dopaminergic neurons in a Cdk5-mediated model of degeneration in Drosophila. Genetically restoring autophagy, or reducing innate immune activation, rescues the dopaminergic neuron loss that occurs due to altered Cdk5 activity. This work revealed an alliance of innate immunity and autophagy that causes neuron loss in Cdk5-mediated neurodegeneration.

Keywords: Anti-microbial peptide; Cdk5; p35; innate immunity; neurodegeneration.

Figure 1.

Schematic summarizing the link between autophagy and immunity in Cdk5-associated neurodegeneration. In affected neurons, inactive autophagosomes signal to the nucleus to enhance transcription of antimicrobial peptides, and these peptides either attack the expressing neuron autonomously, or attack nearby neurons, to induce cell death.