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2017 ; 11
(ä): 59
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RNF146 Inhibits Excessive Autophagy by Modulating the Wnt-?-Catenin Pathway in
Glutamate Excitotoxicity Injury
#MMPMID28321181
Yang Y
; Luo P
; Xu H
; Dai S
; Rao W
; Peng C
; Ma W
; Wang J
; Xu H
; Zhang L
; Zhang S
; Fei Z
Front Cell Neurosci
2017[]; 11
(ä): 59
PMID28321181
show ga
Glutamate induced excitotoxicity is common in diverse neurological disorders.
RNF146 as an E3 ubiquitin ligase protects neurons against excitotoxicity via
interfering with Poly (ADP-ribose) (PAR) polymer-induced cell death
(parthanatos). However, the neuroprotective role of RNF146 has not been fully
understood. We aimed to investigate the role of RNF146 in modulating autophagy in
HT22 cells under glutamate excitotoxicity injury. Here we found that induction of
RNF146 decreased the cellular damage and excitotoxicity induced by glutamate.
RNF146 also suppressed the excessive autophagy, which is detrimental to HT22
cells survival, induced by glutamate or rapamycin treatment. In addition, we find
that Wnt/?-catenin was a negative regulation factor for autophagy in glutamate
excitotoxicity. Over-expression of RNF146 promoted Wnt/?-catenin signaling, which
was related to destabilization of ?-catenin destruction complex. These results
indicated that RNF146 acted as a neuroprotective agent against glutamate-induced
excitatory damage, and this neuroprotection might be at least partly dependent on
the inhibition of excessive autophagy by regulating Wnt/?-catenin signaling.