Protein quality control in neurodegenerative disease

Most proteins undergo posttranslational modification such as acetylation, methylation, phosphorylation, biotinylation, and ubiquitination to regulate various cellular processes. Ubiquitin-targeted proteins from the ubiquitin-proteasome system (UPS) are degraded by 26S proteasome, along with this, deubiquitinating enzymes (DUBs) have specific activity against the UPS through detaching of ubiquitin on ubiquitin-targeted proteins. Balancing between protein expression and degradation through interplay between the UPS and DUBs is important to maintain cell homeostasis, and abnormal expression and elongation of proteins lead to neurodegenerative diseases. Therefore, we are exploring the protein homeostasis network in neurodegenerative diseases to identify therapeutic targets.

UPS-DUB modulation: Screening of  potential therapeutic target for diverse diseases through multi-omics

Several hundreds of E3 ligases lead to substrate degradation, whereas relatively far fewer numbers of DUBs are responsible for detaching or trimming ubiquitins from ubiquitinated proteins. Therefore, each single DUB might have the responsibility for many substrates that participate in many different types of cellular processes. Although many challenges have arisen, now several international research groups have identified DUB inhibitors at the cell, pre-clinical, and clinical levels to improve or identify the targeting of several diseases. As numerous studies have been validated with DUBs so far, DUBs may be one of the most ideal and attractive targets for several diseases and cancers.