Critical Roles of Deubiquitinating Enzymes in the Nervous System and Neurodegenerative Disorders

Post-translational modifications play major roles in the stability, function, and localization of target proteins involved in the nervous system. The ubiquitin-proteasome pathway uses small ubiquitin molecules to degrade neuronal proteins. Deubiquitinating enzymes (DUBs) reverse this degradation and thereby control neuronal cell fate, synaptic plasticity, axonal growth, and proper function of the nervous system. Moreover, mutations or downregulation of certain DUBs have been found in several neurodegenerative diseases, as well as gliomas and neuroblastomas. Based on emerging findings, DUBs represent an important target for therapeutic intervention in various neurological disorders. Here, we summarize advances in our understanding of the roles of DUBs related to neurobiology.