ADAM10-and γ-secretase-dependent cleavage of the transmembrane protein PTPRT attenuates neurodegeneration in the mouse model of Alzheimer's disease

	ADAM10-and γ-secretase-dependent cleavage of the transmembrane protein PTPRT attenuates neurodegeneration in the mouse model of Alzheimer's disease
	Liu, SL; Zhang, ZY; Li, LW; Yao, L; Ma, ZS; Li, JL
	2023
发表期刊	FASEB JOURNAL
ISSN	0892-6638
卷号	37 期号:2
摘要	PTPRT (receptor-type tyrosine-protein phosphatase T), a brain-specific type 1 transmembrane protein, plays an important role in neurodevelopment and synapse formation. However, whether abnormal PTPRT signaling is associated with Alzheimer's disease (AD) remains elusive. Here, we report that Ptprt mRNA expression is found to be downregulated in the brains of both human and mouse models of AD. We further identified that the PTPRT intracellular domain (PICD), which is released by ADAM10- and gamma-secretase-dependent cleavage of PTPRT, efficiently translocates to the nucleus via a conserved nuclear localization signal (NLS). We show that inhibition of nuclear translocation of PICD leads to an accumulation of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a substrate of PTPRT-eventually resulting in neuronal cell death. Consistently, RNA sequencing reveals that overexpression of PICD leads to changes in the expression of genes that are functionally associated with synapse formation, cell adhesion, and protein dephosphorylation. Moreover, overexpression of PICD not only decreases the level of phospho-STAT3(Y705) and amyloid beta production in the hippocampus of APP/PS1 mice but also partially improves synaptic function and behavioral deficits in this mouse model of AD. These findings suggest that a novel role of the ADAM 10- and gamma-secretase-dependent cleavage of PTPRT may alleviate the AD-like neurodegenerative processes.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14129
专题	科研部门_计算生物与医学生态学（马占山）
推荐引用方式 GB/T 7714	Liu, SL,Zhang, ZY,Li, LW,et al. ADAM10-and γ-secretase-dependent cleavage of the transmembrane protein PTPRT attenuates neurodegeneration in the mouse model of Alzheimer's disease[J]. FASEB JOURNAL,2023,37(2).
APA	Liu, SL,Zhang, ZY,Li, LW,Yao, L,Ma, ZS,&Li, JL.(2023).ADAM10-and γ-secretase-dependent cleavage of the transmembrane protein PTPRT attenuates neurodegeneration in the mouse model of Alzheimer's disease.FASEB JOURNAL,37(2).
MLA	Liu, SL,et al."ADAM10-and γ-secretase-dependent cleavage of the transmembrane protein PTPRT attenuates neurodegeneration in the mouse model of Alzheimer's disease".FASEB JOURNAL 37.2(2023).

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