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Conformational Transition of Key Structural Features Involved in Activation of ALK Induced by Two Neuroblastoma Mutations and ATP Binding: Insight from Accelerated Molecular Dynamics Simulations 10.1021/acschemneuro.8b00105 2018-04-17 Deregulated kinase activity of anaplastic lymphoma kinase (ALK) has been observed to be implicated in the development of tumor progression. The activation mechanism of ALK is proposed to be similar to other receptor tyrosine kinases (RTKs), but the distinct s...
Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5) 10.1021/acschemneuro.8b00014 2018-04-17 On the basis of the drug-repositioning and redeveloping strategy, first-generation dual-target inhibitors of acetylcholinesterase (AChE) and phosphodiesterase 5 (PDE5) have been recently reported as a potentially novel therapeutic method for the treatment of ...
New Dopamine D2 Receptor Agonist, [3H]MCL-536, for Detecting Dopamine D2high Receptors in Vivo 10.1021/acschemneuro.8b00096 2018-04-16 Increases in the D2 receptor high affinity state are associated with certain neurological disorders. We synthesized and characterized the high-affinity D2high ligand [3H]MCL-536 in competition binding against the D2/3 agonist R-(−)-N-n-propylnorapomorphine (N...
A Rational Structured Epitope Defines a Distinct Subclass of Toxic Amyloid-beta Oligomers 10.1021/acschemneuro.7b00469 2018-04-16 Oligomers of amyloid-β (AβO) are deemed key in synaptotoxicity and amyloid seeding of Alzheimer’s disease (AD). However, the heterogeneous and dynamic nature of AβO and inadequate markers for AβO subtypes have stymied effective AβO identification and therapeu...
Sarcodonin G Derivatives Exhibit Distinctive Effects on Neurite Outgrowth by Modulating NGF Signaling in PC12 Cells 10.1021/acschemneuro.7b00488 2018-04-13 Sarcodonin G, one of the cyathane diterpenoids isolated from the mushroom Sarcodon scabrosus, possesses pronounced neurotrophic activity but ambiguous mechanical understanding. In this work, sarcodonin G was chosen as a lead compound to prepare a series of 19...
Thioflavin T Interaction with Acetylcholinesterase: New Evidence of 1:1 Binding Stoichiometry Obtained with Samples Prepared by Equilibrium Microdialysis 10.1021/acschemneuro.8b00111 2018-04-13 The aim of the present work was investigation of the fluorescent dye thioflavin T (ThT) binding to acetylcholinesterase (AChE). ThT is an effectively used test for the protease activity, as well as a probe for amyloid fibril formation. Despite the extended an...
Pathway-Specific Alterations of Cortico-Amygdala Transmission in an Arthritis Pain Model 10.1021/acschemneuro.8b00022 2018-04-13 Medial prefrontal cortex (mPFC) and amygdala are closely interconnected brain areas that play a key role in cognitive-affective aspects of pain through their reciprocal interactions. Clinical and preclinical evidence suggests that dysfunctions in the mPFC-amy...
Tyr1-ψ[(Z)CF=CH]-Gly2 Fluorinated Peptidomimetic Improves Distribution and Metabolism Properties of Leu-Enkephalin 10.1021/acschemneuro.8b00085 2018-04-12 Opioid peptides are key regulators in cellular and intercellular physiological responses, and could be therapeutically useful for modulating several pathological conditions. Unfortunately, the use of peptide-based agonists to target centrally located opioid r...
Glycerolipid headgroups control rate and mechanism of SOD1 aggregation and accelerate fibrillization of slowly aggregating ALS mutants 10.1021/acschemneuro.8b00086 2018-04-12 Interactions between superoxide dismutase-1 (SOD1) and lipid membranes might be directly involved in the toxicity and intercellular propagation of aggregated SOD1 in amyotrophic lateral sclerosis (ALS), but the chemical details of lipid-SOD1 interactions and ...
Shedding Light on the Molecular Pathology of Amyloid Plaques in Transgenic Alzheimer’s Disease Mice using Multimodal MALDI Imaging Mass Spectrometry 10.1021/acschemneuro.8b00121 2018-04-12 Senile plaques formed by aggregated amyloid β peptides are one of the major pathological hallmarks of Alzheimer’s disease (AD) which have been suggested to be the primary influence triggering the AD pathogenesis and the rest of the disease process. However, n...

Conformational Transition of Key Structural Features Involved in Activation of ALK Induced by Two Neuroblastoma Mutations and ATP Binding: Insight from Accelerated Molecular Dynamics Simulations

10.1021/acschemneuro.8b00105

2018-04-17

Deregulated kinase activity of anaplastic lymphoma kinase (ALK) has been observed to be implicated in the development of tumor progression. The activation mechanism of ALK is proposed to be similar to other receptor tyrosine kinases (RTKs), but the distinct s...

Novel Tadalafil Derivatives Ameliorates Scopolamine-Induced Cognitive Impairment in Mice via Inhibition of Acetylcholinesterase (AChE) and Phosphodiesterase 5 (PDE5)

10.1021/acschemneuro.8b00014

2018-04-17

On the basis of the drug-repositioning and redeveloping strategy, first-generation dual-target inhibitors of acetylcholinesterase (AChE) and phosphodiesterase 5 (PDE5) have been recently reported as a potentially novel therapeutic method for the treatment of ...

New Dopamine D2 Receptor Agonist, [3H]MCL-536, for Detecting Dopamine D2high Receptors in Vivo

10.1021/acschemneuro.8b00096

2018-04-16

Increases in the D2 receptor high affinity state are associated with certain neurological disorders. We synthesized and characterized the high-affinity D2high ligand [3H]MCL-536 in competition binding against the D2/3 agonist R-(−)-N-n-propylnorapomorphine (N...

A Rational Structured Epitope Defines a Distinct Subclass of Toxic Amyloid-beta Oligomers

10.1021/acschemneuro.7b00469

2018-04-16

Oligomers of amyloid-β (AβO) are deemed key in synaptotoxicity and amyloid seeding of Alzheimer’s disease (AD). However, the heterogeneous and dynamic nature of AβO and inadequate markers for AβO subtypes have stymied effective AβO identification and therapeu...

Sarcodonin G Derivatives Exhibit Distinctive Effects on Neurite Outgrowth by Modulating NGF Signaling in PC12 Cells

10.1021/acschemneuro.7b00488

2018-04-13

Sarcodonin G, one of the cyathane diterpenoids isolated from the mushroom Sarcodon scabrosus, possesses pronounced neurotrophic activity but ambiguous mechanical understanding. In this work, sarcodonin G was chosen as a lead compound to prepare a series of 19...

Thioflavin T Interaction with Acetylcholinesterase: New Evidence of 1:1 Binding Stoichiometry Obtained with Samples Prepared by Equilibrium Microdialysis

10.1021/acschemneuro.8b00111

2018-04-13

The aim of the present work was investigation of the fluorescent dye thioflavin T (ThT) binding to acetylcholinesterase (AChE). ThT is an effectively used test for the protease activity, as well as a probe for amyloid fibril formation. Despite the extended an...

Pathway-Specific Alterations of Cortico-Amygdala Transmission in an Arthritis Pain Model

10.1021/acschemneuro.8b00022

2018-04-13

Medial prefrontal cortex (mPFC) and amygdala are closely interconnected brain areas that play a key role in cognitive-affective aspects of pain through their reciprocal interactions. Clinical and preclinical evidence suggests that dysfunctions in the mPFC-amy...

Tyr1-ψ[(Z)CF=CH]-Gly2 Fluorinated Peptidomimetic Improves Distribution and Metabolism Properties of Leu-Enkephalin

10.1021/acschemneuro.8b00085

2018-04-12

Opioid peptides are key regulators in cellular and intercellular physiological responses, and could be therapeutically useful for modulating several pathological conditions. Unfortunately, the use of peptide-based agonists to target centrally located opioid r...

Glycerolipid headgroups control rate and mechanism of SOD1 aggregation and accelerate fibrillization of slowly aggregating ALS mutants

10.1021/acschemneuro.8b00086

2018-04-12

Interactions between superoxide dismutase-1 (SOD1) and lipid membranes might be directly involved in the toxicity and intercellular propagation of aggregated SOD1 in amyotrophic lateral sclerosis (ALS), but the chemical details of lipid-SOD1 interactions and ...

Shedding Light on the Molecular Pathology of Amyloid Plaques in Transgenic Alzheimer’s Disease Mice using Multimodal MALDI Imaging Mass Spectrometry

10.1021/acschemneuro.8b00121

2018-04-12

Senile plaques formed by aggregated amyloid β peptides are one of the major pathological hallmarks of Alzheimer’s disease (AD) which have been suggested to be the primary influence triggering the AD pathogenesis and the rest of the disease process. However, n...