Neurodegenerative Diseases (DZNE),

For all organisms promoting protein homeostasis is a high priority in order to optimize cel-lular functions and resources. However, there is accumulating evidence that aging leads to a collapse in protein homeostasis and widespread non-disease protein aggregation. This review examines these findings and discusses the potential causes and consequences of this physiological aggregation with age in particular in relation to disease protein aggre-gation and toxicity. Importantly, recent evidence points to unexpected differences in protein-quality-control and susceptibility to protein aggregation between neurons and other cell types. In addition, new insight into the cell-non-autonomous coordination of protein homeostasis by neurons will be presented