In this section, you can access to the latest technical information related to the FUTURE project topic.

Regulation PP2Ac methylation ameliorating autophagy dysfunction caused by Mn is associated with mTORC1/ULK1 pathway

Manganese (Mn) exposure leads to autophagy dysfunction and causes neurodegenerative diseases such as Parkinson's syndrome and Alzheimer's disease. However, the mechanism of neurotoxicity of Mn has been less clear. The methylation of the protein phosphatase 2A catalytic subunit determines the dephosphorylation activity of protein phosphatase and plays an important role in autophagy regulation. In this investigation, we established a model of Mn (0?2000??mol/L) exposure to N2a cells for 12?h, used the PPME-1 inhibitor ABL-127, and constructed an LCMT1-overexpressing N2a cell line. We also regulated the PP2Ac methylation level and explored the effect of PP2Ac methylation on Mn-induced (0?1000??mol/L) N2a cellular autophagy. Our results showed that Mn?>?500??mol/L induced N2a cell damage and increased oxidative stress. Moreover, Mn modulated autophagy in N2a cells by downregulating PP2Ac methylation, which regulated mTORC1 signaling pathway activation. Both ABL-127 and LCMT1 overexpression can upregulate PP2Ac methylation in parallel with ameliorating N2a cell abnormal autophagy induced by Mn, Briefly, the upregulation of PP2Ac methylation can ameliorate the autophagy disorder of N2a by Mn and effectively alleviate Mn-induced cytotoxicity and oxidative stress, indicating that regulation of autophagy is a protective strategy against Mn-induced neurotoxicity.

» Author: Yilu Xu, Lancheng Wei, Shen Tang, Qianqian Shi, Bin Wu, Xiaobo Yang, Yunfeng Zou, Xinhang Wang, Qingqing Ao, Ling Meng, Xuejing Wei, Ning Zhang, Yunqing Li, Chunhua Lan, Muting Chen, Xiyi Li, Cailing Lu

» Publication Date: 01/10/2021

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