In humans, four ubiquitin carboxy-terminal hydrolase (UCH) proteins (UCH-L1, UCH-L3, UCH37/UCH-L5, and BAP1) have been identified, but only UCH-L1 and L3 have been studied in detail . UCH-L1 is a neuronal deubiquitinase that cleaves peptide adducts from the C-terminus of ubiquitin . UCH-L1 is predominantly expressed in the brain . The proteomic analysis of the hippocampus in AβPPswe/PS1dE9 mice shows that the expression of UCH-L1 decreases compared with age-matched wild-type mice . UCH-L1 is downregulated in the brain of patients with Parkinson's disease and AD . The administration of UCH-L1 protein fused to the transduction domain of HIV transactivator (TAT) protein into APP/PS1 model mice of AD provided a protective effect against amyloid-induced neurodegeneration in synaptic function and contextual memory . UCH-L3 is universally expressed in all tissues . UCH-L3-deficient mice exhibit significant impairment in learning and memory using Morris water maze and 8-arm radial maze task . Indeed, our findings showed that UCH-L1 and L3 were downregulated in diabetes-induced dementia. Thus, the decreased expressions of UCH-L1 and L3 could contribute to neurodegeneration, resulting in dementia.