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- W4313366854 abstract "Abstract 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 γ‐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 β 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 γ‐secretase‐dependent cleavage of PTPRT may alleviate the AD‐like neurodegenerative processes." @default.
- W4313366854 created "2023-01-06" @default.
- W4313366854 creator A5032188022 @default.
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- W4313366854 creator A5088699749 @default.
- W4313366854 date "2022-12-30" @default.
- W4313366854 modified "2023-10-12" @default.
- W4313366854 title "<scp>ADAM10</scp>‐ and γ‐secretase‐dependent cleavage of the transmembrane protein <scp>PTPRT</scp> attenuates neurodegeneration in the mouse model of Alzheimer's disease" @default.
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- W4313366854 doi "https://doi.org/10.1096/fj.202201396r" @default.
- W4313366854 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36583697" @default.
- W4313366854 hasPublicationYear "2022" @default.
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