Novel Role of Pin1-Cis P-Tau-ApoE Axis in the Pathogenesis of Preeclampsia and Its Connection with Dementia
Preeclampsia (preE) is a severe multisystem hypertensive syndrome of pregnancy associated with ischemia/hypoxia, angiogenic imbalance, apolipoprotein E (ApoE)-mediated dyslipidemia, placental insufficiency, and inflammation at the maternal–fetal interface. Our recent data further suggest that preE i...
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2024-12-01
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| author | Emmanuel Amabebe Zheping Huang Sukanta Jash Balaji Krishnan Shibin Cheng Akitoshi Nakashima Yitong Li Zhixong Li Ruizhi Wang Ramkumar Menon Xiao Zhen Zhou Kun Ping Lu Surendra Sharma |
| author_facet | Emmanuel Amabebe Zheping Huang Sukanta Jash Balaji Krishnan Shibin Cheng Akitoshi Nakashima Yitong Li Zhixong Li Ruizhi Wang Ramkumar Menon Xiao Zhen Zhou Kun Ping Lu Surendra Sharma |
| author_sort | Emmanuel Amabebe |
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| description | Preeclampsia (preE) is a severe multisystem hypertensive syndrome of pregnancy associated with ischemia/hypoxia, angiogenic imbalance, apolipoprotein E (ApoE)-mediated dyslipidemia, placental insufficiency, and inflammation at the maternal–fetal interface. Our recent data further suggest that preE is associated with impaired autophagy, vascular dysfunction, and proteinopathy/tauopathy disorder, similar to neurodegenerative diseases such as Alzheimer’s disease (AD), including the presence of the cis stereo-isoform of phosphorylated tau (cis P-tau), amyloid-β, and transthyretin in the placenta and circulation. This review provides an overview of the factors that may lead to the induction and accumulation of cis P-tau-like proteins by focusing on the inactivation of peptidyl-prolyl cis–trans isomerase (Pin1) that catalyzes the cis to trans isomerization of P-tau. We also highlighted the novel role of the Pin1-cis P-tau-ApoE axis in the development of preE, and propagation of cis P-tau-mediated abnormal protein aggregation (tauopathy) from the placenta to cerebral tissues later in life, leading to neurodegenerative conditions. In the case of preE, proteinopathy/tauopathy may interrupt trophoblast differentiation and induce cell death, similar to the events occurring in neurons. These events may eventually damage the endothelium and cause systemic features of disorders such as preE. Despite impressive research and therapeutic advances in both fields of preE and neurodegenerative diseases, further investigation of Pin1-cis P-tau and ApoE-related mechanistic underpinnings may unravel novel therapeutic options, and new transcriptional and proteomic markers. This review will also cover genetic polymorphisms in the ApoE alleles leading to dyslipidemia induction that may regulate the pathways causing preE or dementia-like features in the reproductive age or later in life, respectively. |
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| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj-art-4195ea85907741108e17884964567f1a2025-01-24T13:23:46ZengMDPI AGBiomedicines2227-90592024-12-011312910.3390/biomedicines13010029Novel Role of Pin1-Cis P-Tau-ApoE Axis in the Pathogenesis of Preeclampsia and Its Connection with DementiaEmmanuel Amabebe0Zheping Huang1Sukanta Jash2Balaji Krishnan3Shibin Cheng4Akitoshi Nakashima5Yitong Li6Zhixong Li7Ruizhi Wang8Ramkumar Menon9Xiao Zhen Zhou10Kun Ping Lu11Surendra Sharma12Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USADivision of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USADepartment of Molecular Biology, Cell Biology and Biochemistry, Warren Alpert Medical School of Brown University, Providence, RI 02903, USAMitchell Center for Neurodegenerative Diseases, Department of Neurology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USADepartment of Pediatrics, Warren Alpert Medical School of Brown University, Providence, RI 02903, USADepartment of Obstetrics and Gynecology, Faculty of Medicine, University of Toyama, Toyama 930-8555, JapanDepartments of Biochemistry and Oncology, Schulich School of Medicine and Dentistry, Robarts Research Institute, Western University, London, ON N6A 3K7, CanadaDepartments of Biochemistry and Oncology, Schulich School of Medicine and Dentistry, Robarts Research Institute, Western University, London, ON N6A 3K7, CanadaDepartments of Biochemistry and Oncology, Schulich School of Medicine and Dentistry, Robarts Research Institute, Western University, London, ON N6A 3K7, CanadaDivision of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USADepartments of Biochemistry and Oncology, Schulich School of Medicine and Dentistry, Robarts Research Institute, Western University, London, ON N6A 3K7, CanadaDepartments of Biochemistry and Oncology, Schulich School of Medicine and Dentistry, Robarts Research Institute, Western University, London, ON N6A 3K7, CanadaDivision of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USAPreeclampsia (preE) is a severe multisystem hypertensive syndrome of pregnancy associated with ischemia/hypoxia, angiogenic imbalance, apolipoprotein E (ApoE)-mediated dyslipidemia, placental insufficiency, and inflammation at the maternal–fetal interface. Our recent data further suggest that preE is associated with impaired autophagy, vascular dysfunction, and proteinopathy/tauopathy disorder, similar to neurodegenerative diseases such as Alzheimer’s disease (AD), including the presence of the cis stereo-isoform of phosphorylated tau (cis P-tau), amyloid-β, and transthyretin in the placenta and circulation. This review provides an overview of the factors that may lead to the induction and accumulation of cis P-tau-like proteins by focusing on the inactivation of peptidyl-prolyl cis–trans isomerase (Pin1) that catalyzes the cis to trans isomerization of P-tau. We also highlighted the novel role of the Pin1-cis P-tau-ApoE axis in the development of preE, and propagation of cis P-tau-mediated abnormal protein aggregation (tauopathy) from the placenta to cerebral tissues later in life, leading to neurodegenerative conditions. In the case of preE, proteinopathy/tauopathy may interrupt trophoblast differentiation and induce cell death, similar to the events occurring in neurons. These events may eventually damage the endothelium and cause systemic features of disorders such as preE. Despite impressive research and therapeutic advances in both fields of preE and neurodegenerative diseases, further investigation of Pin1-cis P-tau and ApoE-related mechanistic underpinnings may unravel novel therapeutic options, and new transcriptional and proteomic markers. This review will also cover genetic polymorphisms in the ApoE alleles leading to dyslipidemia induction that may regulate the pathways causing preE or dementia-like features in the reproductive age or later in life, respectively.https://www.mdpi.com/2227-9059/13/1/29preeclampsiadementiapeptidyl-prolyl cis–trans isomerasephosphorylated tauapolipoprotein Eautophagy |
| spellingShingle | Emmanuel Amabebe Zheping Huang Sukanta Jash Balaji Krishnan Shibin Cheng Akitoshi Nakashima Yitong Li Zhixong Li Ruizhi Wang Ramkumar Menon Xiao Zhen Zhou Kun Ping Lu Surendra Sharma Novel Role of Pin1-Cis P-Tau-ApoE Axis in the Pathogenesis of Preeclampsia and Its Connection with Dementia Biomedicines preeclampsia dementia peptidyl-prolyl cis–trans isomerase phosphorylated tau apolipoprotein E autophagy |
| title | Novel Role of Pin1-Cis P-Tau-ApoE Axis in the Pathogenesis of Preeclampsia and Its Connection with Dementia |
| title_full | Novel Role of Pin1-Cis P-Tau-ApoE Axis in the Pathogenesis of Preeclampsia and Its Connection with Dementia |
| title_fullStr | Novel Role of Pin1-Cis P-Tau-ApoE Axis in the Pathogenesis of Preeclampsia and Its Connection with Dementia |
| title_full_unstemmed | Novel Role of Pin1-Cis P-Tau-ApoE Axis in the Pathogenesis of Preeclampsia and Its Connection with Dementia |
| title_short | Novel Role of Pin1-Cis P-Tau-ApoE Axis in the Pathogenesis of Preeclampsia and Its Connection with Dementia |
| title_sort | novel role of pin1 cis p tau apoe axis in the pathogenesis of preeclampsia and its connection with dementia |
| topic | preeclampsia dementia peptidyl-prolyl cis–trans isomerase phosphorylated tau apolipoprotein E autophagy |
| url | https://www.mdpi.com/2227-9059/13/1/29 |
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