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Unlabelled: As the principal lipid transporter in the human brain, apolipoprotein E (ApoE) is tasked with the transport and protection of highly vulnerable lipids required to support and remodel neuronal membranes, in a process that is dependent on ApoE receptors. Human allele variants that encode proteins differing only in the number of cysteine (Cys)-to-arginine (Arg) exchanges (ApoE2 [2 Cys], ApoE3 [1 Cys], ApoE4 [0 Cys]) comprise the strongest genetic risk factor for sporadic Alzheimer's disease (AD); however, the molecular feature(s) and resultant mechanisms that underlie these isoform-dependent effects are unknown. One signature feature of Cys is the capacity to form disulfide (Cys-Cys) bridges, which are required to form disulfide bridge-linked dimers and multimers.
View Article and Find Full Text PDFNovel Role of Pin1-Cis P-Tau-ApoE Axis in the Pathogenesis of Preeclampsia and Its Connection with Dementia.
Biomedicines
December 2024
Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.
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.
View Article and Find Full Text PDFThe Apoprotein E4 isotype does not affect the severity of COVID-19 infection and other flu-like syndromes.
J Med Microbiol
January 2025
Departamento de Bioqumica e Imunologia, Instituto de Cincias Biolgicas, Universidade Federal de Minas Gerais.
Apolipoprotein E (ApoE), especially the ApoE4 isotype, is suggested to influence the severity of respiratory viral infections; however, this association is still unclear. The presence of allele ε4 impacts the development of flu-like syndromes. This study aimed to evaluate the impact of the Apo E4 isoform on the severity and duration of flu-like syndromes, including the coronavirus disease COVID-19.
View Article and Find Full Text PDFVariation in lipoprotein(a) response to potent lipid lowering: The role of apolipoprotein (a) isoform size.
J Clin Lipidol
December 2024
Center for the Prevention of Cardiovascular Disease, Leon H. Charney Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine. 530 First Avenue, HCC5, New York, NY 10016, USA. Electronic address:
Background: Lipoprotein(a) [Lp(a)] is a driver of residual cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) decrease Lp(a) with significant heterogeneity in response. We investigated contributors to the heterogeneous response.
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