Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory

作者：Gong Bing; Cao Zixuan; Zheng Ping; Vitolo Ottavio V; Liu Shumin; Staniszewski Agnieszka; Moolman Donna; Zhang Hong; Shelanski Michael^*; Arancio Ottavio

来源：Cell, 2006, 126(4): 775-788.

DOI：10.1016/j.cell.2006.06.046

The neuronal ubiquitin/proteasomal pathway has been implicated in the pathogenesis of Alzheimer's disease (AD). We now show that a component of the pathway, ubiquitin C-terminal hydrolase L1 (Uch-L1), is required for normal synaptic and cognitive function. Transduction of Uch-L1 protein fused to the transduction domain of HIV-transactivator protein (TAT) restores normal enzymatic activity and synaptic function both in hippocampal slices treated with oligomeric A beta and in the APP/PS1 mouse model of AD. Moreover, intraperitoneal injections with the fusion protein improve the retention of contextual learning in APP/PS1 mice over time. The beneficial effect of the Uch-L1 fusion protein is associated with restoration of normal levels of the PKA-regulatory subunit II alpha, PKA activity, and CREB phosphorylation.

• 出版日期2006-8-25