Multimodal analysis of disease onset in Alzheimer's disease using Connectome, Molecular, and genetics data.

Alzheimer's disease (AD) and its related age at onset (AAO) are highly heterogeneous, due to the inherent complexity of the disease. They are affected by multiple factors, such as neuroimaging and genetic predisposition. Multimodal integration of various data types is necessary; however, it has been nontrivial due to the high dimensionality of each modality.

p62/SQSTM1 is required for the protection against endoplasmic reticulum stress-induced apoptotic cell death.

Endoplasmic reticulum (ER) stress is triggered by various cellular stresses that disturb protein folding or calcium homeostasis in the ER. To cope with these stresses, ER stress activates the unfolded protein response (UPR) pathway, but unresolved ER stress induces reactive oxygen species (ROS) accumulation leading to apoptotic cell death. However, the mechanisms that underlie protection from ER stress-induced cell death are not clearly defined.

Ezetimibe, an NPC1L1 inhibitor, is a potent Nrf2 activator that protects mice from diet-induced nonalcoholic steatohepatitis.

Oxidative stress is important for the pathogenesis of nonalcoholic fatty liver disease (NAFLD), a chronic disease that ranges from hepatic steatosis to nonalcoholic steatohepatitis (NASH). The nuclear factor erythroid 2-related factor 2-Kelch-like ECH associated protein 1 (Nrf2-Keap1) pathway is essential for cytoprotection against oxidative stress. In this study, we found that oxidative stress or inflammatory biomarkers and TUNEL positive cells were markedly increased in NASH patients compared to normal or simple steatosis.

Ca(2+) is a Regulator of the WNK/OSR1/NKCC Pathway in a Human Salivary Gland Cell Line.

Wnk kinase maintains cell volume, regulating various transporters such as sodium-chloride cotransporter, potassium-chloride cotransporter, and sodium-potassium-chloride cotransporter 1 (NKCC1) through the phosphorylation of oxidative stress responsive kinase 1 (OSR1) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). However, the activating mechanism of Wnk kinase in specific tissues and specific conditions is broadly unclear. In the present study, we used a human salivary gland (HSG) cell line as a model and showed that Ca(2+) may have a role in regulating Wnk kinase in the HSG cell line.