Results 41 to 50 of about 29,069 (201)

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

GPCRs in CAR‐T Cell Immunotherapy: Expanding the Target Landscape and Enhancing Therapeutic Efficacy

Advanced Science, EarlyView.
Chimeric antigen receptor T cell therapy faces dual challenges of target scarcity and an immunosuppressive microenvironment in solid tumors. This review highlights how G protein‐coupled receptors can serve as both novel targets to expand the therapeutic scope and functional modules to enhance CAR‐T cell efficacy.
Zhuoqun Liu, Yuchen Xiao, Yamin Zhao, Lihe Dai, David J.H. Shih, Shikang Liang, Honglei Tian, Liu Liu, Feng Tian, Bing Liu, Lei Chang, Chao Zhang   +11 more
wiley   +1 more source

Single‐Cell Mitochondrial Lineage Tracing Decodes Fate Decision and Spatial Clonal Architecture in Human Hematopoietic Organoids

Advanced Science, EarlyView.
This study repurposes mitochondrial DNA mutations as endogenous barcodes for lineage tracing in human pluripotent stem cell‐derived organoids. Integrated with transcriptomic and spatial data, it reveals NOTCH‐mediated stromal‐progenitor crosstalk orchestrates clonal dynamics and spatial zonation during early hematopoietic development, offering a non ...
Yan Xue, Junhao Su, Yiming Chao, Lu Liu, Xinyi Lin, Yang Xiang, Mun Kay Ho, Zezhuo Su, Junyi Chen, Zhuojuan Luo, Chengqi Lin, Ruibang Luo, Theo Aurich, Jianfeng Wu, Kelvin Sin Chi Cheung, Yuanhua Huang, Joshua W. K. Ho, Ryohichi Sugimura   +17 more
wiley   +1 more source

Analysis of alteration of p75NTR processing and signalling by PS2 mutation and γ-secretase inhibition

Neurobiology of Disease, 2007
The presenilins (PSs) were identified as causative genes in cases of early-onset familial Alzheimer’s disease (AD) and current evidence indicates that PSs are part of the γ-secretase complex responsible for proteolytic processing of type I membrane ...
Yoshio Ito, Azusa Ishii, A. Peter Passmore, Stephen P. McIlroy   +3 more
doaj   +1 more source

Cytokine‐Engineered Chimeric Antigen Receptor‐T Cell Therapy: How to Balance the Efficacy and Toxicity

Advanced Science, EarlyView.
Cytokine‐engineered CAR‐T cells represent a promising immunotherapy against malignancies due to direct tumor killing and potent immunity response. However, significant toxicities, including CRS and ICANS, have restricted clinical applications. How to keep the risk‐benefit balance of the advanced therapy is of great importance for maximizing the benefit
Xinru Zhang, Gulizeba Aimaiti, Yuanye Guan, Yuzhe Sha, Wei Zhou, Jiefeng Shen, Bo Zhao, Wei‐En Yuan   +7 more
wiley   +1 more source

Activation of the γ-secretase complex and presence of γ-secretase-activating protein may contribute to Aβ42 production in sporadic inclusion-body myositis muscle fibers

Neurobiology of Disease, 2012
The muscle-fiber phenotype of sporadic inclusion-body myositis (s-IBM), the most common muscle disease associated with aging, shares several pathological abnormalities with Alzheimer disease (AD) brain, including accumulation of amyloid-β 42 (Aβ42) and ...
Anna Nogalska, Carla D'Agostino, W. King Engel, Valerie Askanas   +3 more
doaj   +1 more source

Dual‐Target ROS‐Driven Spatiotemporal Senolysis for Vascular Repair and Immune Microenvironment Reprogramming in the Treatment of Ocular Fundus Neovascularization

Advanced Science, EarlyView.
We developed a senolytic approach using procyanidin C1 (PCC1)‐loaded platform, a clinically established and safe hyaluronic acid‐based scaffold, to selectively eliminate senescent endothelial and microglial cells. This dual‐targeting strategy significantly suppresses pathological neovascularization and promotes vascular repair, presenting a safe and ...
Yali Zhou, Tianxing Chen, Peiyu Liu, Kangjia Lv, Yifan Wang, Xiaoqian Wang, Junwei Fang, Chong Chen, Zhaoyang Wang, Fang Wei, Xun Xu   +10 more
wiley   +1 more source

Recent Insights Into Alzheimer's Disease: Advances in Pathophysiology and Therapeutic Strategies

Brain Health, EarlyView.
ABSTRACT Alzheimer's disease (AD) is a complex neurodegenerative disorder driven by interplay among amyloid‐β (Aβ) plaques, tau neurofibrillary tangles, inflammation and comorbid pathologies. Recent advances in biomarkers and therapeutic approvals have reshaped our understanding of its pathophysiology and treatment landscape.
Jiong Shi, Jeffery Cummings, Jacques Touchon, Bruno Vellas   +3 more
wiley   +1 more source

Nontranscriptional Role of Hif-1α in Activation of γ-Secretase and Notch Signaling in Breast Cancer

Cell Reports, 2014
γ-Secretase is composed of four proteins that are obligatory for protease activity: presenilin, nicastrin, Aph1, and Pen-2. Despite the progress toward understanding the function of these individual subunits, there is no information available pertaining ...
Jennifer C. Villa, Danica Chiu, Alissa H. Brandes, Freddy E. Escorcia, Carlos H. Villa, William F. Maguire, Cheng-Jun Hu, Elisa de Stanchina, M. Celeste Simon, Sangram S. Sisodia, David A. Scheinberg, Yue-Ming Li   +11 more
doaj   +1 more source

Presenilin 2 is the predominant γ-secretase in microglia and modulates cytokine release. [PDF]

PLoS ONE, 2010
Presenilin 1 (PS1) and Presenilin 2 (PS2) are the enzymatic component of the γ-secretase complex that cleaves amyloid precursor protein (APP) to release amyloid beta (Aβ) peptide.
Suman Jayadev, Amanda Case, Alison J Eastman, Huy Nguyen, Julia Pollak, Jesse C Wiley, Thomas Möller, Richard S Morrison, Gwenn A Garden   +8 more
doaj   +1 more source