Selective autophagy as the basis of autophagy-based degraders

Degrader technologies, which enable the chemical knockdown of disease-causing proteins, are promising for drug discovery. After two decades research, degraders using ubiquitin-proteasome system (UPS) currently in clinical trials. However, UPS substrates mainly limited to soluble proteins. Autophagy-targeting chimeras and autophagosome-tethering compounds that use autophagy, has functions complementary UPS. They can degrade organelles aggregate-prone making them treatments against age-related conditions such as mitochondrial dysfunction neurodegenerative diseases. The molecular mechanism selective autophagy is an ongoing research topic, explains why autophagy-based were not available until recently. In this review, we introduce four classifications mechanisms facilitate understanding degrader design. (UPS), a proteolytic pathway conserved among eukaryotes, degrades target proteins via large machine, 26S proteasome (Smalle Vierstra, 2004Smalle J. 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