Deubiquitinases in Neurodegeneration

Ubiquitination refers to the conjugation of the ubiquitin protein (a small protein highly conserved among eukaryotes) to itself or to other proteins through differential use of ubiquitin’s seven internal linkage sites or the amino-terminal amino group. By creating different chain lengths, an enormous proteomic diversity may be formed. This creates a signaling system that is central to controlling almost every conceivable protein function, from proteostasis to regulating enzyme function and everything in between. Protein ubiquitination is reversed through the activity of deubiquitinases (DUBs), enzymes that function to deconjugate ubiquitin from itself and protein substrates. DUBs are regulated through several mechanisms, from controlled subcellular localization within cells to developmental and tissue specific expression. Misregulation of DUBs has been implicated in several diseases including cancer and neurodegeneration. Here we present a brief overview of the role of DUBs in neurodegeneration, and as potential therapeutic targets.