Results 121 to 130 of about 692,160 (279)

Macrophage RSAD2 Couples mtDNA Synthesis With a Self‐Amplifying Inflammatory Circuit to Orchestrate Tissue Repair

Advanced Science, EarlyView.
Macrophage RSAD2 dually regulates CMPK2—the rate‐limiting enzyme for mitochondrial DNA synthesis—by suppressing its ubiquitination and promoting its phosphorylation via Csnk2a2 recruitment. This amplifies mtDNA production, which simultaneously activates a cGAS‐STING‐IRF3‐RSAD2 feedforward loop and the NLRP3 inflammasome, driving a self‐sustaining ...
Haomiao Yuan, Shukui Du, Chunfei Li, Xinjie Li, Shuyang Mu, Anran Qu, Hengxu Yan, Chongchong Xu, Jinnong Yang, Jingkai Sun, Yijun Wang, Jiayang Xiao, Fuyuan Zhang, Linlin Wang, Tiegang Li, Rui Zhao, Dawei Guan   +16 more
wiley   +1 more source

Transient Sleep Deprivation Induces Persistent Auditory Neuropathy via ROS‐Initiated Neuroinflammation and BK Channel Suppression

Advanced Science, EarlyView.
Sleep disturbance severity closely tracks hearing loss in a clinical cohort, yet the mechanistic link remains unclear. Acute sleep deprivation is shown to trigger transient cochlear oxidative stress that switches into a self‐sustaining neuroinflammatory state, suppressing BK channels and causing irreversible synaptopathy.
Dan Chen, Ying Ma, Lixuan Huang, Xin Chen, Fanliang Kong, Zhenzhou Qian, Mingyue Guan, Xinlin Wang, Yanyan Yang, Shasha Zhang, Peng Li, Renjie Chai   +11 more
wiley   +1 more source

Toward the Development of Allosteric Inhibitors of IKK2 [PDF]

, 2018
IκB kinase (IKK) is the essential kinase in the activation pathway of NF-κB, a family of transcription factors active in both innate and adaptive immunity. IKK has two catalytic subunits, IKK1 and IKK2, and one scaffolding subunit NEMO.
Hotchkiss, Sonjiala Jackson
core   +1 more source

Scaffold hopping for discovery of N, N-dibenzylcinnamamide (DBCA) derivatives as novel allosteric GSK-3β inhibitors: Design, synthesis and anti-inflammatory evaluation

Results in Chemistry
Glycogen synthase kinase-3β (GSK-3β) has been identified to promote inflammation and its inhibitors have also been proven to treat some inflammatory-mediated diseases in animal models.
Xinyi Zhang, Weiwei Zhao, Feilong Wang, Wei Zhao, Liang Hu, Zhendong Xie, Xueyan Zhu, Peng Zhang, Yong Chu   +8 more
doaj   +1 more source

Reversible, Chemically Gated FRET via Ligand‐Activated Acceptors

Advanced Science, EarlyView.
Fluorogen binding turns the compact FAST tag into a tunable FRET acceptor, with ligand chemistry programming spectral overlap and excited‐state lifetimes. Fluorescence‐lifetime imaging reads out energy transfer through the shortened donor lifetime, while simply adding or washing out the dye switches FRET on and off, reversibly mapping the supramodular ...
Nivedita Singh, Smruti Ranjan Nayak, Sanjay Kumar Mohanty, Aishwarya Hanumantharaju, Amala Shaju, Mini Jose, Aravind Penmatsa, Deepak Nair   +7 more
wiley   +1 more source

Structural Basis of Lymphangiogenic Receptor VEGFR‐3 Activation Mediated by Distinctive Clustering of the Ligand–Receptor Complex

Advanced Science, EarlyView.
VEGF‐C and its receptor VEGFR‐3 are critical for lymphangiogenesis. Cryo‐EM structures of the VEGFR‐3/VEGF‐C ectodomain complex reveal a canonical 2:2 ligand–receptor hetero‐tetramer that further assembles into higher‐order clusters beyond simple receptor dimerization.
Ryeongeun Cho, Jinsook Ahn, Jimin Yang, Dong Sun Lee, Gahi Hong, Sangkyu Lee, Ho Min Kim   +6 more
wiley   +1 more source

An Extracellular Pore‑Targeting Peptide Defines a Designable Allosteric Site in TRPV2

Advanced Science, EarlyView.
Structure‐guided peptide engineering yields Depiv2, a highly potent and subtype‐selective TRPV2 inhibitor that binds to the extracellular pore and remodels it into a closed, non‐conductive state. Depiv2 suppresses pathological cardiac hypertrophy, establishing the TRPV2 outer pore as a designable interface for selective peptide modulation.
Aiqin Zhu, Hongkun Wang, Jiawei Wang, Xiaolu Liu, Aerziguli Aierken, Lizhen Xu, Ping Liang, Fan Yang   +7 more
wiley   +1 more source

Bivalent and Allosteric Inhibitors of Abl and Src Kinase

Protein kinases are key regulators of cell signaling, and their dysregulation is implicated in a wide range of diseases, including cancer. Small-molecule tools that modulate kinase activity are valuable for both therapeutic development and basic research.
Ellis, Jennalise
core   +1 more source

Rational Design of Potent, Small, Synthetic Allosteric Inhibitors of Thrombin

, 2016
Thrombin is a key enzyme targeted by the majority of current anticoagulants that are direct inhibitors. Allosteric inhibition of thrombin may offer a major advantage of finely tuned regulation.
Preetpal Singh Sidhu (705717), Aiye Liang (2055856), Akul Y. Mehta (1315050), Umesh R. Desai (299178), May H. Abdel Aziz (1942039), Qibing Zhou (109189)   +5 more
core   +1 more source

Hederagenin Attenuates Morphine Addiction via GABAA1‐Mediated Modulation of Ca2+–CaMK–CREB Signaling in Ventral Tegmental Dopaminergic Neurons

Advanced Science, EarlyView.
Hederagenin is identified as a GABAA1‐targeting natural compound that suppresses morphine‐associated reward by restraining Ca2+–CaMK–cAMP–CREB signaling in ventral tegmental dopaminergic neurons. RVG29‐modified liposomal delivery further enhances brain accumulation and behavioral efficacy, providing a mechanistically defined strategy for natural ...
Hongyang Jiang, Ziting Zhou, Nannan Xue, Jiasi Deng, Yuanyuan Zhou, Xinying Lv, Yuxuan Wang, Yi Zhang, Haotian Pan, Geyan Xu, Yinkun Tao, Mengran Li, Xin Cui, Hongyue Ma, Qian Wang, Zhigang Lu   +15 more
wiley   +1 more source