Results 41 to 50 of about 45,110 (263)

Autophagy Activators Normalize Aberrant Tau Proteostasis and Rescue Synapses in Human Familial Alzheimer's Disease iPSC‐Derived Cortical Organoids

Advanced Science, EarlyView.
A new cerebrocortical organoid model using isogenic hiPSCs with familial Alzheimer's mutations recapitulates key AD features, including amyloid‐beta and phospho‐Tau aggregation, neuronal hyperexcitability, and synapse loss. Single‐cell RNA‐seq reveals aberrant pathways in excitatory and inhibitory neurons.
Sergio R. Labra, Jadon Compher, Akhil Prabhavalkar, Mireya Almaraz, Claudia Cedeño Kwong, Christine Baal, Maria Talantova, Nima Dolatabadi, Julian Piña‐Sanz, Yubo Wang, Leonard Yoon, Swagata Ghatak, Zi Gao, Yuting Zhang, Dorit Trudler, Lynee Massey, Wei Lin, Anthony Balistreri, Michael Bula, Nicholas J. Schork, Tony S. Mondala, Steven R. Head, Jeffery W. Kelly, Stuart A. Lipton   +23 more
wiley   +1 more source

Research Progress of Endoplasmic Reticulum Stress PERK-eIF2α-AFT4-CHOP Signaling Pathway in Hematological Malignancies

Zhongliu Fangzhi Yanjiu
The biosynthesis and maturation of proteins are primarily regulated by the endoplasmic reticulum in its physiological state. Thus, the disruption of physiological homeostasis initiates the buildup of unfolded and misfolded proteins in the endoplasmic ...
HE Mengke, XU Zizhen, LI Junmin
doaj   +1 more source

HSP90AB1‐Mediated Ubiquitin‐Proteasome Degradation of ITGBL1 Promotes Osteosarcoma Progression by Inhibiting Endoplasmic Reticulum Stress‐Induced Autophagy

Advanced Science, EarlyView.
This study delineates a novel HSP90AB1‐ITGBL1 signaling axis governing osteosarcoma. HSP90AB1 promotes K63‐linked ubiquitination and proteasomal degradation of ITGBL1. Restoring ITGBL1 induces reactive oxygen species‐dependent endoplasmic reticulum stress and pro‐death autophagy, suppressing tumor growth and metastasis.
Zhen Wang, Zixuan Guo, Chengwei Cao, Ziying Wang, Zifu Huang, Xiujuan Zhang, Yushu Zheng, Diankun She, Hao Zhu, Lingfeng Yu, Xuelin Zhao, Dongquan Xiang, Song Liao, Xin He, Xintong Ji, Chengsheng Wu, Cheng‐Xiong Xu, Meng Xu   +17 more
wiley   +1 more source

Decoding the Integrated Stress Response of Pancreatic Cancer: Identifying a Serine‐dependent Tumor Subset Under Metabolic Relationships With CAFs.

Advanced Science, EarlyView.
Researchers identified a pancreatic cancer subset with low global protein synthesis but heightened translation of stress‐response genes like ATF4, rendering cells resistant to chemotherapy and apoptosis. These tumors depend on serine and cysteine from surrounding cancer‐associated fibroblasts (CAFs), which shift to produce serine by curbing collagen ...
Sauyeun Shin, Mehdi Liauzun, Jacobo Solorzano, Morgane Le Bras, Christine Jean, Benjamin Fourneaux, Margaux Dore, Lea Fevrier, Ismahane Belhabib, Alexia Brunel, Cindy Neuzillet, Marion Larroque, Carine Joffre, Stephane Rocchi, Nicolas Fraunhoffer, Aurelie Perraud, Muriel Mathonnet, Vera Pancaldi, Laetitia Linares, Juan Iovanna, Nelson Dusetti, Ola Larsson, Remy Nicolle, Stephane Pyronnet, Corinne Bousquet, Yvan Martineau   +25 more
wiley   +1 more source

Identification and characterization of PERK activators by phenotypic screening and their effects on NRF2 activation.

PLoS ONE, 2015
Endoplasmic reticulum stress plays a critical role to restore the homeostasis of protein production in eukaryotic cells. This vital process is hence involved in many types of diseases including COPD.
Wensheng Xie, Marie Pariollaud, William E Wixted, Nilesh Chitnis, James Fornwald, Maggie Truong, Christina Pao, Yan Liu, Robert S Ames, James Callahan, Roberto Solari, Yolanda Sanchez, Alan Diehl, Hu Li   +13 more
doaj   +1 more source

Brain-Specific Disruption of the eIF2α Kinase PERK Decreases ATF4 Expression and Impairs Behavioral Flexibility

Cell Reports, 2012
Translational control depends on phosphorylation of eIF2α by PKR-like ER kinase (PERK). To examine the role of PERK in cognitive function, we selectively disrupted PERK expression in the adult mouse forebrain.
Mimi A. Trinh, Hanoch Kaphzan, Ronald C. Wek, Philippe Pierre, Douglas R. Cavener, Eric Klann   +5 more
doaj   +1 more source

3D Bioprinted Fat‐Myocardium Model Unravels the Role of Adipocyte Hypertrophy in Atrial Dysfunction

Advanced Science, EarlyView.
A human‐derived 3D bioprinted fat–myocardium model is developed to investigate how adipocyte hypertrophy drives atrial dysfunction in obesity. Palmitate‐induced adipocyte hypertrophy promotes adipose dysfunction that impairs atrial cardiomyocyte metabolism and electrophysiology through both paracrine and direct interactions. This platform recapitulates
Lara Ece Celebi, Pinar Zorlutuna
wiley   +1 more source

Potent and Selective IGF‐IIR‐Recruiting Bifunctional Molecules for Targeted Lysosomal Degradation of Extracellular and Membrane Proteins

Advanced Science, EarlyView.
Lysosome‐targeting chimeras (LYTACs) enable degradation of extracellular and membrane proteins via lysosomal trafficking. We report a novel IGF‐II mutant (Del1–7, Y27L) that selectively engages IGF‐IIR while avoiding IGF‐IR and IR‐A. mutIGF‐II–based LYTACs enhance target internalization and degradation and support a genetically encodable, all‐protein ...
Yuan Zhao, Yaxian Liao, Pengyun Li, Regina Stasser de Gonzalez, Xuankun Chen, Nicholas S. Nieto, Florence M. Brunel, Nick Cox, Joseph Stock, Matthew McHenry, Guangsen Fu, Penghsuan Huang, Wenxin Wu, Deqin Cai, Lingjun Li, Alexander N. Zaykov, Weiping Tang   +16 more
wiley   +1 more source

Hypoxia-Activated PERK Promotes Epithelial-Mesenchymal Transition in Gliomas: A Single-Cell and Spatial Transcriptomic Study With Therapeutic Implications

Frontiers in Bioscience-Landmark
Background: Glioma, the most common brain tumor in adults, exhibits marked hypoxia and invasiveness. Endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR) have been implicated in tumor progression, while epithelial
Jingyan Gu, Yue Kong, Yaohua Liu, Xu Wang, Hongyu Tang, Tingting Zang, Jian Yin, Lianping Gu   +7 more
doaj   +1 more source

Endoplasmic reticulum stress-independent activation of unfolded protein response kinases by a small molecule ATP-mimic

eLife, 2015
Two ER membrane-resident transmembrane kinases, IRE1 and PERK, function as stress sensors in the unfolded protein response. IRE1 also has an endoribonuclease activity, which initiates a non-conventional mRNA splicing reaction, while PERK phosphorylates ...
Aaron S Mendez, Jennifer Alfaro, Marisol A Morales-Soto, Arvin C Dar, Emma McCullagh, Katja Gotthardt, Han Li, Diego Acosta-Alvear, Carmela Sidrauski, Alexei V Korennykh, Sebastian Bernales, Kevan M Shokat, Peter Walter   +12 more
doaj   +1 more source