UCH-L1 (ubiquitin carboxyl-terminal hydrolase L1) is a protein, which plays an important role in ubiquitin-proteasome system. Many previous reports showed the relation between UCH-L1 and neurodegenerative diseases, diabetes, as well as cancer. However, the mechanism still remains unclear. In the aim to investigate the functions and regulatory mechanism of UCH-L1 in living organism, Drosophila melanogaster model was utilized to examine the role of UCH-L1. This chapter provides a summary on recent findings related to the roles of UCH-L1 based on the model. First, abnormal expression of Drosophila ubiquitin carboxyl-terminal hydrolase (dUCH) leads to the defects on fly tissue development and function. Gain function of dUCH in the eye imaginal discs induced a rough eye phenotype in the adult, partly resulting from induction of caspase-dependent apoptosis, upset of photoreceptor cell distribution and ommatidium apical mispatterning. Interestingly, the dUCH overexpression of induced rough eye phenotype was completely recused by co-expression either Sevenless or Draf of the mitogen-activated protein kinase pathway. Besides, knockdown dUCH in dopaminergic neurons resulted in some Parkinson’s disease—like phenotypes in fly. Taken together, those findings in Drosophila model contributed a significant dUCH in tissue development and function.
Part of the book: Drosophila melanogaster
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.
Part of the book: Ubiquitin Proteasome System