Results 121 to 130 of about 4,995,094 (293)

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

Allosteric activation of the glutamate receptor mGlu2 by the serotonin receptor 5-HT2A

Nature Communications
G protein-coupled receptor (GPCR) dimers and higher-order oligomers are the subject of intense debates. The complexes formed between two or more different GPCRs enable the cell to integrate several signals.
Siyu Gai, Li Lin, Jiyong Meng, Yichen Wu, Li Xue, Chanjuan Xu, Qian Sun, Adrià Ricarte, James Dalton, Pedro Renault, Jesús Giraldo, Jean-Philippe Pin, Philippe Rondard, Jianfeng Liu   +13 more
doaj   +1 more source

Co‐activation of Selective Nicotinic Acetylcholine Receptor Subtypes Is Required for Neuroprotection against Alzheimer's Disease

Advanced Science, EarlyView.
ABSTRACT Beta‐amyloid peptide (Aβ)‐induced suppression of hippocampal GABAergic interneuron activity drives hyperexcitability, amyloid pathology, and cognitive impairment in Alzheimer's disease (AD), suggesting that enhancing hippocampal inhibition may be protective.
Rahmi Lee, Gayeon Kim, Ellison R. Black, Seonil Kim   +3 more
wiley   +1 more source

Noncanonical Peloruside A Biosynthesis by an Uncultivated Verrucomicrobiota Symbiont

Angewandte Chemie, EarlyView.
Noncanonical biochemistry of the peloruside PKS characterized in this work, comprising double bond generation by a noncanonical tridomain (blue), acetyl‐CoA recycling (orange), and proofreading systems (purple and yellow). The Z‐double bond is installed by TEB1 through O‐acetylation and acetate elimination. The acyl ligase PelB (AL, orange) selectively
Amy E. Fraley, Michael Rust, Moritz Wagner, Ida R. Hipfinger, Paul J. N. Böhm, Cora L. Dieterich, Christopher M. Field, Michael J. Page, Jeremy G. Owen, Robert A. Keyzers, Shinichi Sunagawa, Jörn Piel   +11 more
wiley   +2 more sources

Structural basis for positive allosteric regulation of CB2 receptor

Nature Communications
The synthetic positive allosteric modulator (PAM) of cannabinoid receptor CB2, Ec21a, exhibits better subtype selectivity and receptor specificity over orthosteric ligands, which holds promise for treating neuropathic pain and seizure without causing ...
Xuehui Wang, Ye Cai, Xin Yang, Shanquan Wu, Jinghong Xian, Jing Wang, Dongsheng Lei, Weimin Li   +7 more
doaj   +1 more source

Machine learning approaches in predicting allosteric sites [PDF]

Allosteric regulation is a fundamental biological mechanism that can control critical cellular processes via allosteric modulator binding to protein distal functional sites.
Zoe, Cournia, Francho, Nerín-Fonz
core   +2 more sources

FBP1‐Mediated Compartmentalization of Glycolytic Enzyme Complexes Suppresses PKM2 Function to Ameliorate MASLD Progression

Advanced Science, EarlyView.
In normal hepatocytes, FBP1 forms compartmentalized complexes with PKM2, ENO1, and LDHA independent of its catalytic activity, inhibiting PKM2 activity and restricting excessive glycolysis. During MASLD progression, FBP1 downregulation markedly reduces the abundance of these complexes and releases the “hijacked” glycolytic enzymes, leading to PKM2 ...
Busong Wang, Yiping Tang, Na Li, Xuening Dai, Jing Wu, Bin Xue, Yuxin Chen, Jingzi Zhang, Lingdong Kong, Chaojun Li, Lei Fang   +10 more
wiley   +1 more source

Beyond Nature's Blueprint: Macrocyclic Peptides Containing Unnatural Amino Acids in Therapeutic Development

Angewandte Chemie, EarlyView.
Strategic incorporation of unnatural amino acids transforms macrocyclic peptides into drug‐like molecules capable of engaging challenging targets. These building blocks enhance stability, permeability, and bioavailability, accelerating the development of next‐generation peptide therapeutics.
Krishna K. Sharma, Komal Sharma, Anku Sharma, Kamya Rao, Rahul Jain, Brett VanVeller   +5 more
wiley   +2 more sources

M1 receptor positive allosteric modulators discovery approaches

Trends in Pharmacological Sciences
The development of M1 muscarinic acetylcholine-receptor-positive allosteric modulators has been hindered by their limited cognitive efficacy and cholinergic side effects. We discuss two unique approaches - low intrinsic agonism and low binding cooperativity - that were developed to address these issues and their therapeutic implications.
Takao Mandai, Arthur A. Simen, Antonio Laurenza, Haruhide Kimura   +3 more
openaire   +2 more sources

Bioenergetic Materials for Tissue Regeneration: Modulating Metabolism to Promote Cellular Anabolism

Advanced Science, EarlyView.
Bioenergetic materials (BEMs) modulate cellular metabolism to promote tissue regeneration. Their principal mechanisms of action include metabolic substrate supplementation, metabolic enzyme modulation, organelle transfer, electrical current regulation, redox homeostasis modulation, and oxygen tension modulation.
Yuchen He, Yuwen Wang, Jonathan F. Gong, Yiting Lei, Fei Jin, Weihong Zhu, Rocky S. Tuan, Zhong Alan Li   +7 more
wiley   +1 more source