Corydaline binds to a druggable pocket of hEAG1 channel and inhibits hepatic carcinoma cell viability.

Ether-à-go-go (EAG) potassium channels play a crucial role in the regulation of neuronal excitability and cancer progression, rendering them potential drug targets for cancer therapy. However, the scarcity of information regarding the selection sites on hEAG1 has posed a challenge in the discovery of new hEAG1 inhibitors. In this study, we introduced a novel natural product, corydaline, which selectively inhibits the hEAG1 channel without sensitivity to other KCNH channels.

Alleviating Neuroinflammation through Photothermal Conjugated Polymer Nanoparticles by Regulating Reactive Oxygen Species and Ca Signaling.

Neuroinflammation is one of the important manifestations of the amyloid β peptide (Aβ) protein-induced neurotoxic signaling pathway in which the aggregation of Aβ causes an increase in reactive oxygen species (ROS) and Ca concentration. Here, near-infrared (NIR) photothermal-responsive conjugated polymer nanoparticles were designed to regulate ROS and Ca signaling to alleviate neuroinflammation. Under 808 nm laser irradiation, the nanoparticles effectively penetrated the blood-brain barrier (BBB) and reduced the aggregation of Aβ and partially disaggregated the aggregates outside the cell, thereby reducing ROS content which downregulated the oxidative stress damage to cells.

Photothermal Conjugated Polymer Nanoparticles for Suppressing Breast Tumor Growth by Regulating TRPA1 Ion Channels.

Cancer cells survive by relying on oxidative stress defense against the accumulation of reactive oxygen species (ROS) during tumor formation. ROS-sensitive TRPA1 ion channels are overexpressed in breast cancer cells and induce a large influx of Ca which upregulates the anti-apoptotic pathway to lead breast cancer cells to produce oxidative stress defense and enhance the resistance to ROS related chemotherapy. Targeting and inhibiting the TRPA1 ion channels are critical for breaking down the oxidative stress defense system and overcoming cellular resistance.

Molecular dynamics simulation of TMEM16A channel: Linking structure with gating.

TMEM16A, the calcium-activated chloride channel, is broadly expressed and plays pivotal roles in diverse physiological processes. To understand the structural and functional relationships of TMEM16A, it is necessary to fully clarify the structural basis of the gating of the TMEM16A channel. Herein, we performed the protein electrostatic analysis and molecular dynamics simulation on the TMEM16A in the presence and absence of Ca.

The Natural Compound Cinnamaldehyde is a Novel Activator of Calcium-Activated Chloride Channel.

Calcium-activated chloride channels (CaCCs) play important roles in a multitude of physiological processes, and in many cells types, TMEM16A was identified as the molecular basis of CaCC. Abnormal CaCC function has been implicated in variety of diseases, which reinforces the need for modulators of CaCCs/TMEM16A. However, there are few specific, clinical modulators of CaCCs.

Hydrocinnamic Acid Inhibits the Currents of WT and SQT3 Syndrome-Related Mutants of Kir2.1 Channel.

Gain of function in mutations, D172N and E299V, of Kir2.1 will induce type III short QT syndrome. In our previous work, we had identified that a mixture of traditional Chinese medicine, styrax, is a blocker of Kir2.

Styrax blocks inward and outward current of Kir2.1 channel.

Kir2.1 plays key roles in setting rest membrane potential and modulation of cell excitability. Mutations of Kir2.

Two Ca(2+)-Binding Sites Cooperatively Couple Together in TMEM16A Channel.

TMEM16A is the molecular basis of calcium-activated chloride channels and shows Ca(2+)-dependent gating. It is critical to understand how the Ca(2+) sensors dynamically control the gate of TMEM16A. However, the detailed mechanism by which the calcium ions bind and open the channel is still obscure.

TMEM16A/B associated CaCC: structural and functional insights.

Calcium-activated chloride channels (CaCCs) play fundamental roles in numerous physiological processes. Transmembrane proteins 16A and 16B (TMEM16A/B) were identified to be the best molecular identities of CaCCs to date. This makes molecular investigation of CaCCs become possible.

Combining fragment homology modeling with molecular dynamics aims at prediction of Ca²⁺ binding sites in CaBPs.

The family of calcium-binding proteins (CaBPs) consists of dozens of members and contributes to all aspects of the cell's function, from homeostasis to learning and memory. However, the Ca²⁺-binding mechanism is still unclear for most of CaBPs. To identify the Ca²⁺-binding sites of CaBPs, this study presented a computational approach which combined the fragment homology modeling with molecular dynamics simulation.