Results 91 to 100 of about 372 (205)

Microglial Deubiquitinase OTUD7B Stabilizes STAT3 to Promote Neuroinflammation and Cognitive Decline in Alzheimer's Disease

Advanced Science, EarlyView.
. ABSTRACT Neuroinflammation driven by microglial activation is a defining feature of Alzheimer's disease (AD), yet the molecular mechanisms sustaining this proinflammatory state remain unclear. Here, we identify the deubiquitinase OTUD7B as a critical regulator of microglial activation and AD pathology.
Luyao Li, Hao Tang, Qin Yu, Yuyang Zhang, Binglu Shi, Ying Kong, Leiyu Xu, Jingjing Shao, Chenghong Hu, Lingyu She, Zhe Wang, Haiyi Chen, Aleksandr V. Samorodov, Gang Cao, Xia Zhao, Yi Wang   +15 more
wiley   +1 more source

Molecular Editing Reveals a Bilobalide Chemotype that Attenuates Prolyl Endopeptidase (PREP)‐Linked Neuroinflammation

Advanced Science, EarlyView.
Molecular editing of bilobalide uncovers BB56, a PREP‐engaging chemotype with enhanced anti‐inflammatory activity in microglia. Integrated CETSA‐MS, SAR, and pathway analyses link BB56 to attenuation of p38 MAPK/NF‐κB and NLRP3‐associated inflammatory signaling, highlighting bilobalide editing as a strategy for developing neuroinflammation‐modulating ...
Chanin Sillapachaiyaporn, Wenjing Wang, Yao Qin, Lili Yan, Stephan Scheeff, Xu He, Qiong Wu, Yue Lin, Jinsai Shang, Xin Ye, Jing Liu, Kailei Sun, Chun Wai Yeung, Junzhe Huang, Zhenghui Chen, Xiaodong Liu, Yiqun Geng, Shannon Wing Ngor Au, Bonaventure Y. Ip, Ho Ko, Billy Wai‐Lung Ng   +20 more
wiley   +1 more source

MKRN1 as a prioritized drug target for postpartum depression: evidence from druggable proteome profiling and multi-layer validation

Translational Psychiatry
Postpartum depression (PPD) is a significant global health concern affecting women, yet effective and innovative therapeutic targets remain limited.
Tingting Jia, Chengsong Yuan, Shiyi Hu, Liangyue Xie, Andi Liu, Fengqin Qin, Yongji He, Chengcheng Zhang   +7 more
doaj   +1 more source

Early Retinal UCHL1 Dysregulation Coupled With Synaptic Loss Reflects Alzheimer's Disease Severity

Advanced Science, EarlyView.
This study identifies synapse‐enriched deubiquitinase UCHL1 as an early Aβ‐responsive regulator of retinal synaptopathy in Alzheimer's disease. Retinal UCHL1 loss accompanies excitatory synapse degeneration, p75NTR activation, and neuroinflammation, and predicts Braak stage and cognitive decline. Aβ42 fibrils trigger synaptic and UCHL1 depletion before
Altan Rentsendorj, Jean‐Philippe Vit, Alexandre Hutton, Yosef Koronyo, Saba Shahin, Edward Robinson, Ernesto Barron, Anthony Rodriguez, Ousman Jallow, Julia Sheyn, Bhakta Prasad Gaire, Lalita Subedi, Miyah R. Davis, Barathan Gnanabharathi, Alexander V. Ljubimov, Stuart L. Graham, Vivek K. Gupta, Mehdi Mirzaei, Debra Hawes, Katlin Silm, Keith L. Black, Lon S. Schneider, Alfredo A. Sadun, Jesse G. Meyer, Dieu‐Trang Fuchs, Maya Koronyo‐Hamaoui   +25 more
wiley   +1 more source

Identifying new biomarkers and potential therapeutic targets for breast cancer through the integration of human plasma proteomics: a Mendelian randomization study and colocalization analysis

Frontiers in Endocrinology
BackgroundThe proteome is a crucial reservoir of targets for cancer treatment. While some targeted therapies have been developed, there are still significant challenges in early diagnosis and treatment, highlighting the need to identify new biomarkers ...
Jingshuang Song, Jingshuang Song, Huawei Yang, Huawei Yang   +3 more
doaj   +1 more source

ZER1 Restrains Pressure Overload‐Induced Cardiac Remodeling by Targeting DVL2 for Gly/N‐Degron‐Dependent Degradation

Advanced Science, EarlyView.
Pressure overload suppresses cardiomyocyte ZER1, weakening CRL2Zer1‐mediated DVL2 degradation and allowing DVL2 accumulation. Elevated DVL2 activates CaMKII‐HDAC4‐MEF2C signaling, drives fetal gene reactivation, and promotes pathological remodeling.
Mingchao Jiang, Zhehao Lin, Lu Chen, Ying Ni, Jun Zhou, Wenjuan Zhang, Huilin Wang, Peifeng Ying, Xiu Lu, Kai Wang, Qingran Kong, Naxin Xu, Dingsheng Zhao, Jianwei Li, Guohui Zhong, Xingchen Meng, Sarkawt Hamad, Junmeng Zheng, Yuan Fu, Rongjiang Qin, Xuran Chu, Shangxuan Li, Youyou Li, Yili Wu, Yi Wang, Weihong Song, Yingxian Li, Shukuan Ling   +27 more
wiley   +1 more source

Proteome-wide Mendelian randomization reveals causal associations between plasma proteins and autoimmune thyroid disease

Scientific Reports
Autoimmune thyroid diseases (AITD) are the most common autoimmune disorders. Identifying new biomarkers and therapeutic targets in plasma proteins is crucial.
Yang Li, Weixi Zhu, Yijing Chen, Qingqing Kang, Ying Zhang, Pan Yang, Shumin Wang, Chao Liu, Yi Zhang, Qiu Zhang   +9 more
doaj   +1 more source

Integrative Omics Analysis Reveals the Regulation of Hypoxia Tolerance in Large Yellow Croaker (Larimichthys crocea) via the Lipoic Acid Synthase (lias) Gene

Advanced Science, EarlyView.
Lipoic acid synthase (lias) can regulate α‐KG levels through lipoylation, thereby negatively regulating HIF‐1α protein levels via PHD under hypoixa. The Hap2 allele of lias exhibits lower expression levels than Hap1, leading to the accumulation of more HIF‐1α protein and thereby enhancing hypoxia tolerance. ABSTRACT Hypoxia stress seriously affects the
Jie Ding, Songpeng Jia, Ran Meng, Xuelei Wang, Xiongfei Wu, Weiliang Shen, Yibo Zhang, Junquan Zhu   +7 more
wiley   +1 more source

MAM‐Localized MANF Counteracts Microinflammatory Stress to Attenuate Mitochondrial Dysfunction and Cataractogenesis in High Myopia

Advanced Science, EarlyView.
Chronic microinflammation in high myopia suppresses MANF in lens epithelial cells. MANF normally resides within MAMs and promotes ubiquitin‐mediated degradation of the ER Ca2+ pump SERCA2. MANF loss causes pathological SERCA2 accumulation, MAM hyperassembly, and disrupted ER‐to‐mitochondria Ca2+ transfer, leading to mitochondrial failure, oxidative ...
Xin Liu, Hao Li, Ching Kang, Dongling Guo, Shuyu Liu, Jiaqi Meng, Zhiqian Huang, Yu Du, Xiangjia Zhu   +8 more
wiley   +1 more source

NIR‐II Light‐Triggered Electron Flow Initiates Cuproptosis‐Centered Thermoelectric‐Immunotherapy for Breast Cancer

Advanced Science, EarlyView.
A NIR‐II light‐activatable thermoelectric nanoreactor converts surface‐bound Cu2+ into bioactive Cu+ via directed electron flow. This spatiotemporally controlled reduction triggers potent cuproptosis and immunogenic cell death, eradicating primary tumors and, together with aPD‐1 therapy, suppressing metastases while establishing durable immune memory ...
Boyu Yuan, Qin Fan, Shushu Chu, Shining Yang, Yuechao Yang, Chenxi Zhang, Jinqiao Zhang, Xinran Qu, Yiju Wei, Xin Wang, Ziliang Dong   +10 more
wiley   +1 more source