**Yoshihisa Watanabe 1,\*, Katsutoshi Taguchi <sup>2</sup> and Masaki Tanaka 2,\***


Received: 5 August 2020; Accepted: 2 September 2020; Published: 2 September 2020

**Abstract:** Ubiquitin signals play various roles in proteolytic and non-proteolytic functions. Ubiquitin signals are recognized as targets of the ubiquitin–proteasome system and the autophagy–lysosome pathway. In autophagy, ubiquitin signals are required for selective incorporation of cargoes, such as proteins, organelles, and microbial invaders, into autophagosomes. Autophagy receptors possessing an LC3-binding domain and a ubiquitin binding domain are involved in this process. Autophagy activity can decline as a result of genetic variation, aging, or lifestyle, resulting in the onset of various neurodegenerative diseases. This review summarizes the selective autophagy of neurodegenerative disease-associated protein aggregates via autophagy receptors and discusses its therapeutic application for neurodegenerative diseases.

**Keywords:** ubiquitin; autophagy; neurodegenerative diseases; ubiquitin–proteasome system; autophagy–lysosome pathway
