Carboxyl terminus of heat-shock cognate 70-interacting protein degrades tau regardless its phosphorylation status without affecting the spatial memory of the rats.
Accumulation of the hyperphosphorylated tau is a hallmark pathological event for the formation of neurofibrillary tangles in Alzheimer disease (AD). Until now, there is no effective way to antagonize this accumulation. Recently, it has been reported that carboxyl terminus of Hsc70-interacting protein (CHIP) is the specific tau E3 ligase and it mediates tau degradation in vitro. However, the nature of CHIP on in vivo tau degradation is not fully understood. Here, we demonstrated that hippocampal transfection of CHIP plasmid in rats could reach a time-dependent elevated expression of CHIP mRNA and protein in 24 h. Concomitantly, expression of exogenous CHIP could promote the degradation of the hyperphosphorylated tau induced by overactivation of glycogen synthase kinase-3 (GSK-3) or inhibition of protein phosphatase-2A (PP-2A) in the rat brains and N2A cells. CHIP also degraded tau in normal rats regardless the phosphorylation status of tau proteins. Though CHIP overexpression was not able to improve significantly the spatial memory retention deficits induced by overactivation of GSK-3, it did not cause significant damage to the memory function in normal rats. These results suggest that CHIP may degrade tau both in physiological and pathological conditions without affecting the behavior of the rats, implying that overexpression of CHIP may antagonize tau accumulation in the AD brains.
Zhang
Y-J
YJ
Pathophysiology Department, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Xu
Y-F
YF
Liu
X-H
XH
Li
D
D
Yin
J
J
Liu
Y-H
YH
Chen
X-Q
XQ
Wang
J-Z
JZ
D000818:Animals; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013037:Spatial Behavior / Q000502:physiology*; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D050883:HSC70 Heat-Shock Proteins; D012333:RNA, Messenger; D016875:tau Proteins; D044767:Ubiquitin-Protein Ligases