The gad mouse: a Window into UPS-Related Neurodegeneration and the Function of the Deubiquitinating Enzyme UCH-L1

The gad mouse: a Window into UPS-Related Neurodegeneration and the Function of the Deubiquitinating Enzyme UCH-L1

Deubiquitinating enzymes reversibly control the state of protein ubiquitination. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is exclusively expressed in neuronal cells and in the testis/ovary. UCH-L1 is a constituent of cellular aggregates that are commonly observed in neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). The UCH-L1 gene reportedly causes familial PD and is the basis for the gracile axonal dystrophy ( gad ) mouse. These facts suggest that the function of UCH-L1 is closely related to the survival and maintenance of the neuron. This review summarized the role of UCH-L1 in the pathogenesis of neurodegenerative diseases, with particular emphasis on the gad mouse, which offers unique insights into the relationship of UPS to neurodegeneration in an in vivo setting.

Deubiquitinating enzymes reversibly control the state of protein ubiquitination. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is exclusively expressed in neuronal cells and in the testis/ovary. UCH-L1 is a constituent of cellular aggregates that are commonly observed in neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). The UCH-L1 gene reportedly causes familial PD and is the basis for the gracile axonal dystrophy ( gad ) mouse. These facts suggest that the function of UCH-L1 is closely related to the survival and maintenance of the neuron. This review summarized the role of UCH-L1 in the pathogenesis of neurodegenerative diseases, with particular emphasis on the gad mouse, which offers unique insights into the relationship of UPS to neurodegeneration in an in vivo setting.