Ubiquitin Carboxyl-Terminal Hydrolase L1 in Parkinson’s Disease

Ubiquitin plays the crucial roles to maintain the ubiquitin proteasome system (UPS) functions, which were suggested that involved in Parkinson’s diease (PD). Ubiquitin C-terminal hydrolase L1 (UCHL1), which was detected in Lewy bodies of nerve cells in PD brains, plays an important role for maintaining ubiquitin pool in UPS. The first UCHL1 mutation (UCHL1I93M) was found in two siblings of a PD family. By contrast, UCHL1S18Y mutation was recognized to reduce the risk of developing PD by its specific antioxidant protective function. The studies of UCHL1 in mouse models showed that lack of UCHL1 resulted in motor ataxia, degeneration of axons, and instability of free ubiquitin level. Transgenic mice expressing UCHL1I93M mutant exhibited dopaminergic neuron (DA) degeneration in MPTP-treated conditions. In this chapter, we provide a summary on recent findings related to roles of UCH-L1 in PD. Knockdown dUCH, a homolog of human UCHL1, in fly dopaminergic neuron resulted as some Parkinson’s disease—like phenotype such as: (1) the underdevelopment and/or degeneration of DA neurons; (2) the shortage of dopamine in the brain; and (3) the locomotor dysfunctions. Those finding indicated that dUCH (ortholog of human UCH-L1 in Drosophila) plays an important role in Parkinson’s disease