Multitargeted Aza-Arylcarboxamides for Neurodegenerative Diseases: Potent Histamine H3 Receptor Ligands with Anticholinesterase and Metal-Chelating Activities [0.03%]
用于治疗神经退行性疾病的多靶点氮杂芳基羰基胺：具有抗乙酰胆碱酯酶和金属螯合活性的组胺H3受体配体
Flavia B Lopes,Tobias Werner,Izilda A Bagatin et al.
Flavia B Lopes et al.
Neurodegenerative diseases are conditions characterized by neuronal loss in the nervous system, leading to diverse symptoms associated with complex pathological mechanisms. Dysregulation of metal ions such as iron and copper is linked to ox...
Proteomic Characterization of Striatal Neurabin Interactome and Its Sex Specific Impact on Motor Behavior [0.03%]
纹状体Neurabin蛋白互作谱的蛋白质组学分析及其对性别特异的运动行为的影响
Nikhil R Shah,Wesley B Corey,Camden N Harris et al.
Nikhil R Shah et al.
The striatum serves as the primary input nucleus of the basal ganglia. Reversible protein phosphorylation in the post synaptic density (PSD) of medium spiny neurons (MSNs) modulates inputs from striatal afferents. The context dependent regu...
4-(1-Methylethoxy)- N-(2-methyl-8-quinolinyl)-benzamide (CDN1163) Attenuates Glutamate-Induced Excitotoxicity by Suppressing ER Stress and Restoring Mitochondrial Dynamics in N2a Cells [0.03%]
4-异丙氧基-N-(2-甲基-8-喹啉基)-苯甲酰胺（CDN1163）通过抑制内质网应激和恢复神经母细胞瘤细胞中线粒体动力学来缓解谷氨酸诱导的兴奋毒性
Vikrant Rahi,Swapnil Sharma,Ravinder K Kaundal
Vikrant Rahi
Excessive glutamate release during excitotoxic events such as stroke and neurodegeneration leads to elevated mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane depolarization, contributing to dysfunction of th...
Griess's Reagent-Based Azo Compounds Ameliorate Multifaceted Toxicity and Ferroptosis in Alzheimer's Disease [0.03%]
基于Griess试剂的偶氮化合物可缓解阿尔茨海默病的多功能毒性和铁死亡
Ashish Kumar,Tanmay Mondal,Madhu Ramesh et al.
Ashish Kumar et al.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and a growing public health concern globally due to the lack of effective treatments. The primary pathological characteristics of AD include the accumulation of amyloid-β...
A Dual Approach To Combat Alzheimer's Disease through Concomitant h BChE Inhibition and S1R Activation [0.03%]
通过同时抑制hBChE和激活S1R双重途径对抗阿尔茨海默病
Kora Reichau,Lucie Crouzier,Eleonora Poeta et al.
Kora Reichau et al.
Alzheimer's disease (AD) remains an incurable neurodegenerative disorder, requiring novel therapeutic strategies. We developed multitarget-directed ligands designed to inhibit human butyrylcholinesterase (hBChE) and activate the sigma-1 rec...
Ester Prodrug NLRP3 Inflammasome Inhibitor NT-0796 is Brain Active due to Activation by Local Expression of Carboxylesterase-1 [0.03%]
由于局部表达的羧酸酯酶-1活化酯类前药NLRP3炎性小体抑制剂NT-0796在脑中具有活性
Zsofia Digby,Christine Diamond,Heather Wescott et al.
Zsofia Digby et al.
NLRP3 inflammasome activation has been implicated in the pathogenesis of human disorders, including a number of neurodegenerative diseases of the central nervous system. Pharmacological inhibition of NLRP3-mediated neuroinflammation via a b...
Calretinin Contributes to Trigeminal Neuropathic Pain Downstream of Cavα2δ1 [0.03%]
Calretinin参与Cavα2δ1下游的三叉神经病理性疼痛产生
Yu-Quan Wang,Wen-Bo Liu,Wen-Qiang Cui et al.
Yu-Quan Wang et al.
Trigeminal neuralgia is a debilitating neuropathic pain disorder characterized by facial hypersensitivity, yet its underlying molecular mechanisms remain incompletely understood. Using a mouse model of partial infraorbital nerve transection...
Discovery of 7-(Pyridin-3-yl)thieno[3,2- b]pyridine-5-carboxamides as Negative Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 [0.03%]
发现7-（吡啶-3-基）噻吩并[3,2-b]吡啶-5-羧酸酰胺类元为代谢型谷氨酸受体5亚型的负向变构调节剂
Scott H Henderson,Anna E Ringuette,David L Whomble et al.
Scott H Henderson et al.
Herein, we report the structure-activity relationship (SAR) to develop novel mGlu5 negative allosteric modulator (NAM) scaffolds devoid of the aryl/heterobiaryl acetylene moiety found in many historic mGlu5 NAMs, which has been linked to me...
Discovery of VU6025733 (AG06827): A Highly Selective, Orally Bioavailable, and Structurally Distinct M4 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator (PAM) with Robust In Vivo Efficacy [0.03%]
VU6025733（AG06827）的发现：一种高度选择性、可口服生物利用且结构独特的M4胆碱能受体阳性变构调节剂，具有强大的体内疗效
Alison R Gregro,Charlotte Park,Madeline F Long et al.
Alison R Gregro et al.
This work describes progress toward an M4 PAM preclinical candidate. The SAR to address potency, clearance, subtype selectivity, CNS exposure, and P-gp efflux are detailed within. A novel 1-(7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl...
Emil Axell,Andreas Carlsson,Max Lindberg et al.
Emil Axell et al.
Intracellular deposits of neurofibrillary tau tangles and extracellular Aβ plaques are closely associated with Alzheimer's disease. The mapping of thermodynamic parameters, including solubility limits, indicates when a protein forms amyloi...