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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., (© 2022 Federation of American Societies for Experimental Biology.)

Primary cilium, first described in the 19th century in different cell types and organisms by Alexander Ecker, Albert Kolliker, Aleksandr Kowalevsky, Paul Langerhans, and Karl Zimmermann (Ecker, 1844; Kolliker, 1854; Kowalevsky, 1867; Langerhans, 1876; Zimmermann, 1898), play an essential modulatory role in diverse aspects of nervous system development and function. The primary cilium, sometimes referred to as the cell's 'antennae', can receive wide ranging inputs from cellular milieu, including morphogens, growth factors, neuromodulators, and neurotransmitters. Its unique structural and functional organization bequeaths it the capacity to hyper-concentrate signaling machinery in a restricted cellular domain approximately one-thousandth the volume of cell soma. Thus enabling it to act as a signaling hub that integrates diverse developmental and homestatic information from cellular milieu to regulate the development and function of neural cells. Dysfunction of primary cilia contributes to the pathophysiology of several brain malformations, intellectual disabilities, epilepsy, and psychiatric disorders. This review focuses on the most essential contributions of primary cilia to cerebral cortical development and function, in the context of neurodevelopmental disorders and malformations. It highlights the recent progress made in identifying the mechanisms underlying primary cilia's role in cortical progenitors, neurons and glia, in health and disease. A future challenge will be to translate these insights and advances into effective clinical treatments for ciliopathies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The present study was aimed to investigate whether herpes simplex virus type 1 (HSV-1) could infect human retinal pigment epithelial (RPE) cells in vitro and the effects of HSV-1 on the growth of human RPE cells., Methods: RPE cell line D407 was infected with HSV-1 F strain at a multiplicity of infection of 5. The susceptibility to HSV-1 was assessed by the detection of viral DNA using the polymerase chain reaction (PCR), and viral antigen using immunofluorescence staining. At indicated times, contrast-phase microscope was used to record the morphological changes of HSV-1 infection of RPE cells. Cell proliferation was measured by MTT assay. Cell apoptosis and cell cycle were detected by flow cytometry., Results: HSV-1 infected RPE cells successfully in vitro. The contrast-phase microscope revealed that cytopathic effects (CPE) were first observed at 8 h post-infection. The infected cells became slender and shrinking. At 24 h post-infection, nearly all the cells displayed CPE changes. Occasionally multinucleated giant cells were found. At 48 h, the infected cells became round, some even detached from the culture flask. Cell proliferation were dramatically inhibited by HSV-1 at 24 h and 48 h post-infection, and the inhibition ratio were (16.37 +/- 3.28)% and (47. 91 +/- 6.39)% respectively. Furthermore, HSV-1 could perturb the cell cycle in the infected cells, and had no effect on cell apoptosis., Conclusions: Our data suggested that RPE cells are susceptible to HSV-1. HSV-1 can inhibit cell proliferation and perturb the cell cycle in the infected cells.