UCHL1 is a member of the peptidase C12 family and a thiol protease th at hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin to generate the ubiquitin monomer. UCHL1 is expressed in the neurons and in cells of the diffuse neuroendocrine system. Mutations in UCHL1 may be associated with Parkinson disease. The ligase and hydrolase activities of UCHL1 may play roles in proteasomal protein degradation, a process critical for neuronal health. Inhibition of UCHL1 in mouse hippocampal slices reduces normal synaptic function and long-term potentiation. PKA-CREB pathway mediates the effects of UCHL1 on Amyloid-beta-induced synaptic dysfunction and Uchl1 also reversed the inhibition of CREB phosphorylation induced by Amyloid-beta.
