Eukaryotic cells have two major systems to degrade toxic and misfolded proteins: the ubiquitin-proteasome system (UPS), and the autophagy-lysosomal pathway. The UPS is the route by which a cell degrades soluble, short-lived and misfolded proteins. Such misfolded proteins are tagged by ubiquitin and further targeted to the proteasome for degradation. Evidence has been provided that UPS function has been inhibited in polyQ diseases , implying that polyQ proteins cannot be degraded by the UPS system 68, , so that misfolded polyQcontaining proteins must be degraded by autophagy. In brief, the process includes formation of a dual membrane, engulfing structures such as misfolded proteins, organelles and other substrates, forming autophagosomes, which further fuse with lysosomes so that lysosomal enzymes degrade the contents. The functional significance of the relation of UPS dysregulation and protein aggregation to disease pathophysiology remains unclear.