Results 111 to 120 of about 137,279 (309)

Nicotinic acid mononucleotide is an allosteric SARM1 inhibitor promoting axonal protection

, 2021
SARM1 is an inducible NAD(+) hydrolase that is the central executioner of pathological axon loss. Recently, we elucidated the molecular mechanism of SARM1 activation, demonstrating that SARM1 is a metabolic sensor regulated by the levels of NAD(+) and ...
Gu, Weixi, Milbrandt, J, DiAntonio, Aaron, Sasaki, Y, Kobe, Bostjan, Gu, W, Ve, Thomas, Zhu, J, Sasaki, Yo, DiAntonio, A, Milbrandt, Jeffrey, Kobe, B, Shi, Yun, Zhu, Jian, Ve, T, Shi, Y   +15 more
core   +1 more source

Molecular Glue cc‐885 Inhibits VHL‐Deficient Clear Cell Renal Cell Carcinoma via ETS1 Degradation

Advanced Science, EarlyView.
VHL‐deficient kidney cancer lacks effective treatments. This study reveals that the molecular glue degrader cc‐885 hijacks the cellular recycling system to selectively destroy the oncogenic protein ETS1, effectively killing VHL‐mutant tumors. Combining CC‐885 with the approved drug belzutifan achieves powerful synergy, offering a promising new ...
Taowei Yang, Qihao Li, Kun Ye, Kezhi Liu, Mi Zhou, Minyu Chen, Lican Liao, Kangbo Huang, Zhu Wang, Qiong Deng, Jieyan Wang, Meiyu Jin, Xu Chen, Hui Liang, Jiaxing Zhang, Junhang Luo   +15 more
wiley   +1 more source

Conservation, mutation density, and disease associations of allosteric and non-allosteric proteins involved in disease.

, 2022
Kinases and drug targets are shown separately. A-C) Allosteric proteins are characterised by a somewhat higher conservation than non-allosteric proteins.
György Abrusán (3389270), Michael Inouye (103694), David B. Ascher (1358214)   +2 more
core   +1 more source

From Inducing Allosteric Signaling to Exploring the Allosteric Effect of SNPS and Allosteric Polymorphism [PDF]

Biophysical Journal, 2020
Wei-Ven Tee, Enrico Guarnera, Zhen Wah Tan, Igor N. Berezovsky   +3 more
openaire   +1 more source

Dose‐Dependent Reprogramming of Chromatin Accessibility by SOX4 Drives the Transcriptional Response to Iron Overload

Advanced Science, EarlyView.
This study demonstrates that iron overload triggers widespread chromatin compaction and transcriptional repression in human granulosa cells, recapitulating features of endometriosis. The epigenetic reprogramming is orchestrated by a TFEB‐SOX4‐SWI/SNF axis, with SOX4 acting as a central, dosage‐sensitive regulator.
Feifei Li, Yaoqiu Wu, Guangyu Yang, Jingyi Lai, Xiaoyue Sun, Liyan Wang, Xiaoli Li, Jing Zhang, Qingxue Zhang, Hui Chen, Haiyan Lin, Bingxiang Xu, Junfeng Zhang, Hailong Wang, Anming Meng, Chunwei Cao   +15 more
wiley   +1 more source

Targeting Supramolecular Active Complexes of Nav1.7/Nav1.8 to Relieve Chronic Neuropathic Pain

Advanced Science, EarlyView.
In mice and patients with severe chronic neuropathic pain (NP), Nav1.7, Nav1.8, TrkB, and five cytoskeletal proteins form supramolecular active complexes (SMACs) with polygonal lattice structures as noxious signal amplifiers in dorsal root ganglion (DRG) neurons.
Liting Sun, Hang Xian, Yunxin Shi, Taotan Yang, Hongyan Shuai, Wenchao Hu, Siying Fei, Miao Xu, Taoyuan Yang, Ruilong Xia, Ting Wen, Fengting Zhu, Yan Fu, Yang Li, Wei Xia, Ran Qian, Yuanying Liu, Zhicheng Tian, Lamei Li, Qian Zhou, Lize Xiong, Rui Cong, Ceng Luo, Shengxi Wu, Xiafeng Shen, Xin Yu, Rou‐Gang Xie, Changgeng Peng   +27 more
wiley   +1 more source

Development of allosteric modulators of GPCRs for treatment of CNS disorders

Neurobiology of Disease, 2014
The discovery of allosteric modulators of G protein-coupled receptors (GPCRs) provides a promising new strategy with potential for developing novel treatments for a variety of central nervous system (CNS) disorders.
Hilary Highfield Nickols, P. Jeffrey Conn   +1 more
doaj   +1 more source

Divergent Roles of mGlu2 and mGlu3 Receptors in Amyloid‐β Production and Cognitive Dysfunctions in Alzheimer's Disease

Advanced Science, EarlyView.
This study explores the opposing effects of the mGluR2 and mGluR3 receptors on amyloid precursor protein processing. mGluR2 promotes amyloidogenic cleavage, while mGluR3 favors non‐amyloidogenic pathways. Using a brain‐penetrant nanobody as a mGluR2 positive allosteric modulator, the study uncovers how its chronic activation aggravates amyloid‐β burden
Pierre‐André Lafon, Mireille Elodie Tsitokana, Ugo Guy Alenda, Yen‐Ling Lian, Clémentine Eva Philibert, Mathieu Oosterlaken, Marta Cimadevila, Gaëlle Dudon, Jessica Monnic, Salomé Roux, Julie Bessié, Séverine Diem, Franck Vandermoere, Laurent Prézeau, Patrick Chames, Julie Kniazeff, Sylvie Claeysen, Anaïs Menny, Jean‐Philippe Pin, Véronique Perrier, Jianfeng Liu, Philippe Rondard   +21 more
wiley   +1 more source

Entrapment of hemocyanin conformers as a tool for the definition of the structural model of cooperativity [PDF]

, 2013
Allostery has been established as a fundamental mechanism of regulation in most biological processes (Changeux, 2012). The most studied allosteric protein is hemoglobin, that has long been considered a paradigm for the investigation of allostery and ...
Minute, Fabrizio
core  

Kinsenoside Targets IDH1 to Restore Microglial Immune‐Metabolic Homeostasis for Alzheimer's Disease Therapy

Advanced Science, EarlyView.
Dysregulated TCA cycle contributes to Alzheimer's disease (AD) pathogenesis. Here, we show that microglial isocitrate dehydrogenase 1 (IDH1) is a critical driver. Elevated IDH1 disrupts citrate metabolism and mitochondrial function, exacerbating AD pathology.
Qianqian Li, Yajin Liao, Yan‐bo Zhao, Hongxing Wu, Tong Jin, Shuoshuo Li, Yuhan Liu, Peng Li, Songying Ouyang, Zekai Li, YuTing Xia, Qian Hua, Rui‐Yuan Pan, Zengqiang Yuan   +13 more
wiley   +1 more source