All cells are endowed with two catabolic pathways for degrading protein: the ubiquitinproteasome
system (UPS) and autophagy. While these routes of protein degradation were long
considered to be parallel and complementary systems, new evidence has revealed interaction between
the UPS and autophagy, suggesting a coordinated relationship that becomes critical in times of
cellular stress. Here we introduce the basics and parallels of the UPS and autophagy, review the
evidence for cross-regulation of the two systems, and highlight their emerging coordinated
relationship. Throughout, we review the evidence suggesting that impairment of autophagy could
contribute to the initiation or progression of age-related neurodegeneration.
