Viorica Raluca Contu, Yaichiro Kotake, Takashi Toyama, Katsuhiro Okuda, Masatsugu Miyara, Shuichiro Sakamoto, Shigeyoshi Samizo, Seigo Sanoh, Yoshito Kumagai and Shigeru Ohta Endogenous neurotoxic dopamine derivative covalently binds to Parkinson's disease-associated ubiquitin C-terminal hydrolase L1 and alters its structure and function Journal of Neurochemistry 130
We investigated the interaction between ubiquitin C-terminal hydrolase L1 (UCH-L1) and the brain endogenous parkinsonism inducer 1-(3′,4′-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline (3′,4′DHBnTIQ). Our results indicate that 3′,4′DHBnTIQ binds to UCH-L1 specifically at cysteine 152 and induces its aggregation. 3′,4′DHBnTIQ also inhibits the hydrolase activity of UCH-L1. Catechol-modified as well as insoluble UCH-L1 were detected in the midbrains of MPTP-treated Parkinson's disease (PD) model mice. Conjugation of UCH-L1 by neurotoxic endogenous compounds like 3′,4′DHBnTIQ might play a key role in onset and progression of PD.
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