RNF146 Inhibits Excessive Autophagy by Modulating the Wnt-β-Catenin Pathway in Glutamate Excitotoxicity Injury

Yang, Yuefan and Luo, Peng and Xu, Haoxiang and Dai, Shuhui and Rao, Wei and Peng, Cheng and Ma, Wenke and Wang, Jiu and Xu, Hongyu and Zhang, Lei and Zhang, Sai and Fei, Zhou (2017) RNF146 Inhibits Excessive Autophagy by Modulating the Wnt-β-Catenin Pathway in Glutamate Excitotoxicity Injury. Frontiers in Cellular Neuroscience, 11. ISSN 1662-5102

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Abstract

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/β-catenin was a negative regulation factor for autophagy in glutamate excitotoxicity. Over-expression of RNF146 promoted Wnt/β-catenin signaling, which was related to destabilization of β-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/β-catenin signaling.

Item Type: Article
Subjects: STM Open Press > Medical Science
Depositing User: Unnamed user with email support@stmopenpress.com
Date Deposited: 27 Jun 2023 06:06
Last Modified: 24 Jun 2024 04:40
URI: http://journal.submissionpages.com/id/eprint/1681

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