Enabling systemic identification and functionality profiling for Cdc42 homeostatic modulators.

Maintaining body homeostasis is the ultimate key to health. There are rich resources of bioactive materials for the functionality of homeostatic modulators (HMs) from both natural and synthetic chemical repertories. HMs are powerful modern therapeutics for human diseases including neuropsychiatric diseases, mental disorders, and drug addiction (e.

G-Protein Signaling in Alzheimer's Disease: Spatial Expression Validation of Semi-supervised Deep Learning-Based Computational Framework.

Systemic study of pathogenic pathways and interrelationships underlying genes associated with Alzheimer's disease (AD) facilitates the identification of new targets for effective treatments. Recently available large-scale multiomics datasets provide opportunities to use computational approaches for such studies. Here, we devised a novel sease ene entification (digID) computational framework that consists of a semi-supervised deep learning classifier to predict AD-associated genes and a protein-protein interaction (PPI) network-based analysis to prioritize the importance of these predicted genes in AD.

Enabling Systemic Identification and Functionality Profiling for Cdc42 Homeostatic Modulators.

Unlabelled: Homeostatic modulation is pivotal in modern therapeutics. However, the discovery of bioactive materials to achieve this functionality is often random and unpredictive. Here, we enabled a systemic identification and functional classification of chemicals that elicit homeostatic modulation of signaling through Cdc42, a classical small GTPase of Ras superfamily.

RhoA-LIMK Signaling Axis Reveals Rostral-Caudal Plane and Spatial Dysregulation in the Brain of Alzheimer's Disease Mouse Models.

Background: RhoA signaling is widely reported to be dysregulated in Alzheimer's disease (AD), but its therapeutic targeting demonstrated mixed outcomes. We hypothesize that the activation and inactivation states of RhoA and LIMK are different in the cortex and in subregions of hippocampus along the rostral-caudal dimensions.

Objective: We intended to elucidate the plane and spatial dependent RhoA signaling in association with AD.

Crosstalk between the Rho and Rab family of small GTPases in neurodegenerative disorders.

Neurodegeneration is associated with defects in cytoskeletal dynamics and dysfunctions of the vesicular trafficking and sorting systems. In the last few decades, studies have demonstrated that the key regulators of cytoskeletal dynamics are proteins from the Rho family GTPases, meanwhile, the central hub for vesicle sorting and transport between target membranes is the Rab family of GTPases. In this regard, the role of Rho and Rab GTPases in the induction and maintenance of distinct functional and morphological neuronal domains (such as dendrites and axons) has been extensively studied.

Can GPR4 Be a Potential Therapeutic Target for COVID-19?

Coronavirus disease 19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first emerged in late 2019 and has since rapidly become a global pandemic. SARS-CoV-2 infection causes damages to the lung and other organs. The clinical manifestations of COVID-19 range widely from asymptomatic infection, mild respiratory illness to severe pneumonia with respiratory failure and death.

The Proton-Sensing GPR4 Receptor Regulates Paracellular Gap Formation and Permeability of Vascular Endothelial Cells.

GPR4 is a pH-sensing G protein-coupled receptor highly expressed in vascular endothelial cells and can be activated by protons in the inflamed tissue microenvironment. Herein, we report that acidosis-induced GPR4 activation increases paracellular gap formation and permeability of vascular endothelial cells through the G/Rho GTPase signaling pathway. Evaluation of GPR4 in the inflammatory response using the acute hindlimb ischemia-reperfusion mouse model revealed that GPR4 mediates tissue edema, inflammatory exudate formation, endothelial adhesion molecule expression, and leukocyte infiltration in the inflamed tissue.