Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory.
Cell
; 126(4): 775-88, 2006 Aug 25.
Article
in En
| MEDLINE
| ID: mdl-16923396
ABSTRACT
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 Abeta 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 IIalpha, PKA activity, and CREB phosphorylation.
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Database:
MEDLINE
Main subject:
Recombinant Fusion Proteins
/
Amyloid beta-Protein Precursor
/
Synaptic Transmission
/
Ubiquitin Thiolesterase
/
Alzheimer Disease
/
Memory
Limits:
Animals
/
Humans
Language:
En
Year:
2006
Type:
Article