UCHL1 is a multifunctional protein expressed at high concentrations in neurons in the brain and spinal cord. UCHL1 plays important roles in regulating the level of cellular free ubiquitin and redox state as well as the degradation of select proteins. This review focuses on the potential role of UCHL1 in the pathogenesis of neurodegenerative diseases and brain injury and recovery. Subjects addressed in the review include 1) Normal physiological functions of UCHL1. 2) Posttranslational modification sites and splice variants that alter the function of UCHL1 and mouse models with mutations and deletions of UCHL1. 3) The hypothesized role and pathogenic mechanisms of UCHL1 in neurodegenerative diseases and brain injury. 4) Potential therapeutic strategies targeting UCHL1 in these disorders.
Keywords: Brain injury; Neurodegeneration; Protein degradation; Ubiquitin C-terminal hydrolase 1; Ubiquitin-proteasome pathway.
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