A unique compound ameliorating endoplasmic reticulum stress and insulin resistance by binding to β tubulin.

Insulin is secreted by the pancreatic β-cells and regulates glucose uptake. Endoplasmic reticulum (ER) stress is known to induce insulin resistance. Identifying novel compounds, which can ameliorate ER stress and insulin resistance may be beneficial in the treatment of diabetes.

Midnolin, a Genetic Risk Factor for Parkinson's Disease, Promotes Neurite Outgrowth Accompanied by Early Growth Response 1 Activation in PC12 Cells.

Parkinson's disease (PD) is an age-related progressive neurodegenerative disease. Previously, we identified midnolin () as a genetic risk factor for PD. Although copy number loss increases the risk of PD, the molecular function of MIDN remains unclear.

Recent progress on action and regulation of anorexigenic adipokine leptin.

Organismal energy balance is controlled by inter-tissue communication mediated by the nervous system and hormones, the disruption of which causes metabolic syndrome exemplified by diabetes and obesity. Fat-storing adipose tissue, especially those located in subcutaneous white adipose tissue, secretes leptin in a proportion of fat mass, inhibiting the accumulation of organismal fat by suppressing appetite and promoting energy expenditure. With a prevalence of obesity that exhibits hyperleptinemia, most of the investigation on leptin has been focused on how it works and how it does not, which is expected to be a clue for treating obesity.

Alkannin Attenuates Amyloid Aggregation and Alzheimer's Disease Pathology.

Alzheimer's disease (AD) is a neurodegenerative disease that is accompanied by memory decline and cognitive dysfunction. Aggregated amyloid formation and accumulation may be one of the underlying mechanisms of the pathophysiology of AD. Therefore, compounds that can inhibit amyloid aggregation may be useful for treatment.

Neurobehavioral characteristics of mice with mutations as models of IDD23 and KBG syndromes.

Genomic analysis has revealed that the genes for various chromatin regulators are mutated in many individuals with neurodevelopmental disorders (NDDs), emphasizing the important role of chromatin regulation in nervous system development and function. Chromatin regulation is mediated by writers, readers, and erasers of histone and DNA modifications, with such proteins being defined by specific domains. One of these domains is the SET domain, which is present in enzymes that catalyze histone methylation.

Homocysteine causes neuronal leptin resistance and endoplasmic reticulum stress.

Abnormally high serum homocysteine levels have been associated with several disorders, including obesity, cardiovascular diseases or neurological diseases. Leptin is an anti-obesity protein and its action is mainly mediated by the activation of its Ob-R receptor in neuronal cells. The inability of leptin to induce activation of its specific signaling pathways, especially under endoplasmic reticulum stress, leads to the leptin resistance observed in obesity.

COOH-terminal fragment of APP interacts with p62, forms an aggregate, and induces autophagic degradation in Alzheimer's cell model.

Alzheimer's disease is an intractable disease, and the accumulation of amyloid β in the brain is thought to be involved in the onset of the disease. Additionally, abnormal protein accumulation due to autophagic deficiency may also be involved in disease progression. Autophagy involves a mechanism called selective autophagy.

SPT16 ubiquitylation by DCAF14-CRL4 regulates FACT binding to histones.

The histone chaperone complex FACT comprises SPT16 and SSRP1 and contributes to DNA replication, transcription, and repair, but how it plays such various roles is unclear. Here, we show that human SPT16 is ubiquitylated at lysine-674 (K674) by the DCAF14-CRL4 ubiquitin ligase. K674 is located in the middle domain of SPT16, and the corresponding residue of the yeast ortholog is critical for binding to histone H3.

Insulin Enhances Gene Expression of , a Novel Genetic Risk Factor for Parkinson's Disease, via Extracellular Signal-Regulated Kinase, Phosphoinositide 3-Kinase and Multiple Transcription Factors in SH-SY5Y Cells.

Parkinson's disease (PD) is the second most common neurodegenerative disease. Although many monogenic variants have been identified that cause familial PD, most cases are sporadic and the mechanisms of sporadic PD onset remain unclear. We previously identified () as a novel genetic risk factor for PD in a Japanese population.

Thermal Proteome Profiling Reveals Glutathione Peroxidase 4 as the Target of the Autophagy Inducer Conophylline.

Conophylline (CNP) is a vinca alkaloid extracted from the plant. It has been reported that CNP induces autophagy in a mammalian target of rapamycin-independent manner, and thereby inhibits protein aggregation. However, the mode of action of CNP in inducing autophagy remains unknown.

The possible role of biochanin A in ameliorating endoplasmic reticulum stress-induced leptin resistance.

Leptin plays an important role in energy intake and body weight homeostasis. Leptin is secreted mainly from white adipose tissue and circulates in the bloodstream, inhibiting food intake by activating the leptin receptor expressed on hypothalamic neurons. Recent studies have demonstrated leptin resistance as the main factor involved in the development of obesity.

Central Acting Hsp10 Regulates Mitochondrial Function, Fatty Acid Metabolism, and Insulin Sensitivity in the Hypothalamus.

Mitochondria are critical for hypothalamic function and regulators of metabolism. Hypothalamic mitochondrial dysfunction with decreased mitochondrial chaperone expression is present in type 2 diabetes (T2D). Recently, we demonstrated that a dysregulated mitochondrial stress response (MSR) with reduced chaperone expression in the hypothalamus is an early event in obesity development due to insufficient insulin signaling.

Possible Involvement of MyD88 in Regulating Stress Response in Mice.

Myeloid differentiation primary response 88 (MyD88) is an adapter protein of the toll-like receptor (TLR) family that regulates innate immune function. Here, we identified a novel role of MyD88 in regulating stress response. MyD88 deficiency decreased immobility time in the forced swim test without affecting locomotor activity in mice.

Grapefruit juice exerts anti-osteoporotic activities in a prednisolone-induced osteoporosis rat femoral fracture model, possibly via the RANKL/OPG axis.

This study aimed to shed light on the protective and therapeutic anti-osteoporotic effects and mechanisms of action of grapefruit juice (GFJ) on prednisolone-induced osteoporosis a rat femoral fracture model. We found that treating rats with GFJ before and/or after prednisolone-induced osteoporosis resulted in increased bone density, total mineral content, and calcium content to counteract the osteoporotic effects of prednisolone. In parallel, the histological and ultrastructural results of the GFJ-treated groups correlated well with enhanced breaking strength of femurs subjected to a constant load.

Anticancer effect of nor-wogonin (5, 7, 8-trihydroxyflavone) on human triple-negative breast cancer cells via downregulation of TAK1, NF-κB, and STAT3.

Background: Nor-wogonin, a polyhydroxy flavone, has been shown to possess antitumor activity. However, the mechanisms responsible for its antitumor activity are poorly studied. Herein, we investigated the mechanisms of nor-wogonin actions in triple-negative breast cancer (TNBC) cells.

Possible involvement of 4-hydroxy-2-nonenal in the pathogenesis of leptin resistance in obesity.

Insensitivity to the antiobesity hormone, leptin, has been suggested to be involved in the pathogenesis of obesity. However, the pathological mechanisms underlying the development of leptin resistance are not well-understood. This study aimed to examine the pathological mechanisms of leptin resistance in obesity.

Immobilization stress induces XBP1 splicing in the mouse brain.

Cells activate the unfolded protein response (UPR) to cope with endoplasmic reticulum (ER) stress. In the present study, we investigated the possible involvement of psychological stress on UPR induction in the mouse brain. When mice were exposed to immobilization stress for 8 h, XBP1 mRNA splicing was significantly induced in the hippocampus, cortex, hypothalamus, cerebellum, and brain stem.

Incorporation of the Endoplasmic Reticulum Stress-Induced Spliced Form of XBP1 mRNA in the Exosomes.

It is known that endoplasmic reticulum (ER) and nucleus communicate with each other to cope with ER stress. However, the mechanisms through which extracellular transmission of ER stress occurs remain unexplored. When the ER stress-induced unfolded protein response (UPR) is activated, the X-box binding protein 1 (XBP1) mRNA is spliced by inositol-requiring enzyme-1α (IRE1α) to produce the spliced form of XBP1 (sXBP1).

TERT enhances the survival rate of human fibroblasts under endoplasmic reticulum, Golgi apparatus, and lysosomal stresses.

Objective: The exposure of organelles, such as the endoplasmic reticulum (ER), Golgi apparatus (GA), and lysosomes, to stress activates death mechanisms. Recently, telomerase reverse transcriptase (TERT) has been shown to be involved in cell survival. However, the relationship between TERT and the stress responses is still unclear.

[Implementation and Evaluation of Genetic Testing Seminars about Lifestyle-related Disease Prevention in Pharmacy Insurance-The Need for Cooperation between the Pharmacy and the University in Genetic Testing].

 A seminar titled "Implementation and evaluation of genetic testing of lifestyle-related disease genes" was held for pharmacists, medical clerks, and clerks of pharmacy insurance, with the aim of holding seminars led by pharmacists for the general public (including patients) in the future. The subject of the seminar was single nucleotide polymorphisms in obesity-related genes and alcohol metabolism-related genes. The purpose of the seminar was to contribute to the prevention of lifestyle-related diseases of the general public.

Mechanisms of the action of adenine on anti-allergic effects in mast cells.

Introduction: Mast cells play an important role in allergic responses.

Methods: We herein demonstrated the mechanisms of inhibitory effect of adenine on IgE/antigen-induced degranulation and TNF-α release in mast cells.

Results: We found that these effects were dependent on the amino group of adenine because purine only weakly inhibited degranulation.

Loss of Stearoyl-CoA Desaturase-1 Activity Induced Leptin Resistance in Neuronal Cells.

The lack of response to leptin's actions in the brain, "leptin resistance," is one of the main causes of the pathogenesis of obesity. However, although high-fat diets affect sensitivity to leptin, the underlying mechanisms of leptin resistance are still an enigma. Here we examined the effect of excess saturated fatty acids (SFAs) on leptin signaling in human neuronal cells.

Endospanin1 affects oppositely body weight regulation and glucose homeostasis by differentially regulating central leptin signaling.

Unlabelled: The hypothalamic arcuate nucleus (ARC) is a major integration center for energy and glucose homeostasis that responds to leptin. Resistance to leptin in the ARC is an important component of the development of obesity and type 2 diabetes. Recently, we showed that Endospanin1 (Endo1) is a negative regulator of the leptin receptor (OBR) that interacts with OBR and retains the receptor inside the cell, leading to a decreased activation of the anorectic STAT3 pathway.