Results 111 to 120 of about 131,252 (300)

A Novel Pak1 Activator Ameliorates ER Stress for HFpEF Therapy

Advanced Science, EarlyView.
Chronic metabolic stress is a major contributor to HFpEF progression. Under prolonged metabolic stress, Pak1 activity becomes impaired, contributing to disrupted ER proteostasis, cardiomyocyte apoptosis, fibrosis, and diastolic dysfunction. Mechanistically, Pak1 overexpression activates the ERK1/2–MNK1–eIF4E signaling axis, promotes translational ...
Honglin Xu, Hongyuan Zhang, Tayyiba Azam, Susanne S. Hille, Yingjuan Liu, Min Zi, Jiaqing Lang, He Yu, Yujia Cao, Bernard D. Keavney, Tamer M. A. Mohamed, Jessica M. Miller, Riham R. E. Abouleisa, Ming Xu, Elizabeth J. Cartwright, Oliver J. Müller, Ming Lei, Xin Wang   +17 more
wiley   +1 more source

Virtual Screening and Molecular Dynamics Study of Potential Negative Allosteric Modulators of mGluR1 from Chinese Herbs

Molecules, 2015
The metabotropic glutamate subtype 1 (mGluR1), a member of the metabotropic glutamate receptors, is a therapeutic target for neurological disorders. However, due to the lower subtype selectivity of mGluR1 orthosteric compounds, a new targeted strategy ...
Ludi Jiang, Xianbao Zhang, Xi Chen, Yusu He, Liansheng Qiao, Yanling Zhang, Gongyu Li, Yuhong Xiang   +7 more
doaj   +1 more source

Endogenous, exogenous and novel allosteric modulators of ligand-gated ion channels [PDF]

, 2019
The central nervous system is a web of neuronal communication, mediated through excitatory and inhibitory signals. These signals are mediated in part by the amino acid neurotransmitters glutamate, GABA and glycine, which are ligands for specific ligand ...
Pflanz, Natasha Christina
core   +1 more source

DDX3x Regulates NINJ1 Transcription via Histone Lactylation in Sepsis Associated‐Acute Kidney Injury

Advanced Science, EarlyView.
This study identifies a potential therapeutic approach for sepsis‐associated acute kidney injury (SA‐AKI). We found that during SA‐AKI, reduced expression of DDX3x in renal tubular epithelial cells mediates histone delactylation, which in turn upregulates NINJ1 transcription and triggers tubular cell death. Conversely, Odetiglucan confers protection by
Hongyu Liang, Jihong Jiang, Huanxin Yin, Chunyan Liu, Hongjun Huang, Yan Luo, Minmin Zhu, Qiuyun Wang   +7 more
wiley   +1 more source

Concentration dependence of the interaction of two allosteric modulators binding each to its own allosteric site.

, 2019
Upper row, simulation of tracer binding (ordinate) in the presence two allosteric modulators A and B each binding to its own site, where A is either positive (left) or negative (right) and B is negative allosteric modulator.
Esam E. El-Fakahany (339452), Alena Randáková (339451), Jan Jakubík (339449), Vladimír Doležal (339453)   +3 more
core   +1 more source

Transcription Factor HOXC11 Drives Colorectal Cancer Progression and Metastasis via CAMK2A‐Dependent CXCL5 Upregulation

Advanced Science, EarlyView.
HOXC11 drives colorectal cancer progression by transcriptionally activating CAMK2A, which triggers NF‐κB–dependent CXCL5 upregulation. CXCL5–CXCR2 signaling further reinforces HOXC11 expression through the ERK1/2–SP1 axis, forming a prometastatic positive feedback loop that is effectively disrupted by combined CAMK2A and CXCR2 inhibition.
Qingyang Sun, Hengjie Xu, Sheng Yang, Jiahui Zhou, Chuanxin Tian, Hongxu Nie, Chi Jin, Tuo Wang, Zhihao Chen, Junwei Tang, Yifei Feng, Xiaowei Wang, Yueming Sun   +12 more
wiley   +1 more source

Two allosteric modulators each binding to its own site.

, 2019
Allosteric interaction between tracer X and allosteric modulators A and B at receptor R. Each allosteric modulator binds to its own site, with cooperative interaction between the two sites.
Esam E. El-Fakahany (339452), Alena Randáková (339451), Jan Jakubík (339449), Vladimír Doležal (339453)   +3 more
core   +1 more source

Selective Modulation of OTUB1 Noncanonical Function via a bioPhosTAC Strategy

Advanced Science, EarlyView.
This work positions the versatile performance of the peptide‐based bioPhosTAC platform for dissecting phosphorylation‐dependent biology and expanding the scope of induced‐proximity technologies. We demonstrated that selective manipulation of a tyrosine phosphorylation site is sufficient to propagate coordinated cellular consequences.
Seung Un Seo, Seon Min Woo, Minhyeong Choi, Soeun Rhee, Simmyung Yook, Donghyuk Shin, Kwang‐Su Park, Taeg Kyu Kwon   +7 more
wiley   +1 more source

Entropy‐Driven Physical Amplification in Multivalent Biosensing

Advanced Science, EarlyView.
Detecting scarce molecules usually demands enzymatic amplification such as PCR. A statistical‐mechanical theory now reveals a purely physical alternative: distributing a fixed binding strength over more linker arms exponentially lowers the concentration at which multivalent sensors switch on.
Yuhan Peng, Xiuyang Xia, Ran Ni
wiley   +1 more source

Structural and dynamic insights into the activation of the μ-opioid receptor by an allosteric modulator

Nature Communications
G-protein-coupled receptors (GPCRs) play pivotal roles in various physiological processes. These receptors are activated to different extents by diverse orthosteric ligands and allosteric modulators. However, the mechanisms underlying these variations in
Shun Kaneko, Shunsuke Imai, Tomomi Uchikubo-Kamo, Tamao Hisano, Nobuaki Asao, Mikako Shirouzu, Ichio Shimada   +6 more
doaj   +1 more source