Dietary impact on neuronal autophagy control and brain health

Abstract

Autophagy is the major intracellular system which is critical for the removal of harmful protein aggregates and malfunctioning organelles. Dysfunctional autophagy is associated with a multitude of human diseases, such as protein aggregation in Alzheimer’s disease and non-successful aging. Major interest exists in the dietary manipulation of the autophagy pathway activity, so as to tune the cell’s protein degradation capabilities and to prevent cell death onset. It has recently become clear that the machinery required to degrade protein cargo has a distinct activity level which can be altered through specific dietary modulation. Moreover, this activity may differ from that of the proteinaceous cargo. Overall, brain health and successful aging are characterized by limited protein aggregation, with a distinct molecular signature of maintained autophagy function. However, it is largely unclear how to control autophagy through dietary interventions with a precision that would allow to maintain minimal levels of toxic proteins, preserving neuronal cell viability and proteostasis. In this chapter, we carefully dissect the relationship between autophagy- modulating drugs, including caloric restriction mimetics and their impact on neuronal autophagy, in the context of preserving brain health.