HIF-1α stabilization inhibits Japanese encephalitis virus propagation and neurotoxicity via autophagy pathways.

Japanese encephalitis (JE) is a widespread flavivirus that induces brain inflammation and affects the central nervous system (CNS). Deferoxamine, an iron chelator, has shown promising results in stabilizing HIF-1α, a protein that improves hypoxic conditions, offers protective effects against neurological, and neurodegenerative diseases. This study aimed to assess the impact of HIF-1α stabilization during JEV infection using SH-SY5Y neuroblastoma cell lines as a model.

Melatonin-mediated calcineurin inactivation attenuates amyloid beta-induced apoptosis.

Alzheimer's disease (AD) is the most common age-related progressive neurodegenerative disorder. The accumulation of amyloid beta-peptide is a neuropathological marker of AD. While melatonin is recognized to have protective effects on aging and neurodegenerative disorders, the therapeutic effect of melatonin on calcineurin in AD is poorly understood.

Melatonin inhibits Japanese encephalitis virus replication and neurotoxicity via calcineurin-autophagy pathways.

Background: Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that has no specific treatment except for supportive medical care. JEV is a neurotropic virus that affects the nervous system and triggers inflammation in the brain.

Methods: Melatonin is used as a sleep-inducing agent in neurophysiology and may serve as a protective agent against neurological and neurodegenerative diseases.

Antiviral activity of prion protein against Japanese encephalitis virus infection in vitro and in vivo.

Flaviviruses are a major cause of viral diseases worldwide, for which effective treatments have yet to be discovered. The prion protein (PrPc) is abundantly expressed in brain cells and has been shown to play a variety of roles, including neuroprotection, cell homeostasis, and regulation of cellular signaling. However, it is still unclear whether PrPc can protect against flaviviruses.

Calcineurin, Calcium-Dependent Serine-Threonine Phosphatase Activation by Prion Peptide 106-126 Enhances Nuclear Factor-κB-Linked Proinflammatory Response through Autophagy Pathway.

Prion diseases are mortal neurodegenerative pathologies that are caused by the accumulation of abnormal prion protein (PrPSc) in the brain. Recent advances reveal that calcineurin may play a critical role in regulating nuclear factor kappa B (NF-κB) in the calcium-calmodulin pathway. However, the exact mechanism by calcineurin remains unclear.

Calcineurin Activation by Prion Protein Induces Neurotoxicity via Mitochondrial Reactive Oxygen Species.

Prion diseases are caused by PrPsc accumulation in the brain, which triggers dysfunctional mitochondrial injury and reactive oxygen species (ROS) generation in neurons. Recent studies on prion diseases suggest that endoplasmic reticulum (ER) stress induced by misfolding proteins such as misfolded prion protein results in activation of calcineurin. Calcineurin is a calcium-related protein phosphatase of type 2B that exists in copious quantities in the brain and acts as a critical nodal component in the control of cellular functions.

The antidiabetic drug troglitazone protects against PrP (106‑126)‑induced neurotoxicity via the PPARγ‑autophagy pathway in neuronal cells.

Prion diseases, which involve the alteration of cellular prion protein into a misfolded isoform, disrupt the central nervous systems of humans and animals alike. Prior research has suggested that peroxisome proliferator‑activator receptor (PPAR)γ and autophagy provide some protection against neurodegeneration. PPARs are critical to lipid metabolism regulation and autophagy is one of the main cellular mechanisms by which cell function and homeostasis is maintained.

Prion peptide-mediated calcium level alteration governs neuronal cell damage through AMPK-autophagy flux.

Background: The distinctive molecular structure of the prion protein, PrPsc, is established only in mammals with infectious prion diseases. Prion protein characterizes either the transmissible pathogen itself or a primary constituent of the disease. Our report suggested that prion protein-mediated neuronal cell death is triggered by the autophagy flux.

Human prion protein-mediated calcineurin activation induces neuron cell death via AMPK and autophagy pathway.

It is usually accepted that prion proteins induce apoptosis in nerve cells. However, the mechanisms of PrP-neurotoxicity are not completely clear. Calcineurin is a Ca/calmodulin-dependent phosphatase.

Inhibition of Autophagy by Captopril Attenuates Prion Peptide-Mediated Neuronal Apoptosis via AMPK Activation.

Accumulation of prion protein (PrPc) into a protease-resistant form (PrPsc) in the brains of humans and animals affects the central nervous system. PrPsc occurs only in mammals with transmissible prion diseases. Prion protein refers to either the infectious pathogen itself or the main component of the pathogen.

Telmisartan generates ROS-dependent upregulation of death receptor 5 to sensitize TRAIL in lung cancer via inhibition of autophagy flux.

Telmisartan broadly used for the treatment of hypertension that is also known for its anticancer properties. TRAIL has the potential to kill tumor cells with minimal toxicity in normal cells by binding to death receptors, DR4 and DR5. Unfortunately, these TRAIL-death receptors have failed as most human cancers are resistant to TRAIL-mediated apoptosis.

Glipizide sensitizes lung cancer cells to TRAIL-induced apoptosis via Akt/mTOR/autophagy pathways.

The combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with subsidiary agents is a promising anticancer strategy to conquer TRAIL resistance in malignant cells. Glipizide is a second-generation oral hypoglycemic medicine for the cure of type II diabetes because of its capability to selectively stimulate insulin secretion from β-cells. In this study, we revealed that glipizide could trigger TRAIL-mediated apoptotic cell death in human lung adenocarcinoma cells.

PPARγ activation by troglitazone enhances human lung cancer cells to TRAIL-induced apoptosis via autophagy flux.

Members of the tumor necrosis factor (TNF) transmembrane cytokine superfamily, such as TNFα and Fas ligand (FasL), play crucial roles in inflammation and immunity. TRAIL is a member of this superfamily with the ability to selectively trigger cancer cell death but does not motive cytotoxicity to most normal cells. Troglitazone are used in the cure of type II diabetes to reduce blood glucose levels and improve the sensitivity of an amount of tissues to insulin.

SIRT1, a Class III Histone Deacetylase, Regulates LPS-Induced Inflammation in Human Keratinocytes and Mediates the Anti-Inflammatory Effects of Hinokitiol.

Skin inflammation is a response of the immune system to infection and injury. In this study, we report that hinokitiol, a tropolone-related natural compound that exhibits antioxidant, anti-inflammatory, and anticancer properties in various cell types, can modulate the inflammatory responses of primary human keratinocytes challenged with lipopolysaccharide (LPS). Hinokitiol treatment inhibited LPS-mediated up-regulation of proinflammatory factors including tumor necrosis factor alpha, IL-6, and prostaglandin E (PGE).

Autophagy flux induced by ginsenoside-Rg3 attenuates human prion protein-mediated neurotoxicity and mitochondrial dysfunction.

Mitochondrial quality control is a process by which mitochondria undergo successive rounds of fusion and fission with dynamic exchange of components to segregate functional and damaged elements. Removal of mitochondrion that contains damaged components is accomplished via autophagy. In this study, we investigated whether ginsenoside Rg3, an active ingredient of the herbal medicine ginseng that is used as a tonic and restorative agent, could attenuate prion peptide, PrP (106-126)-induced neurotoxicity and mitochondrial damage.

Activation of autophagic flux by epigallocatechin gallate mitigates TRAIL-induced tumor cell apoptosis via down-regulation of death receptors.

Epigallocatechin gallate (EGCG) is a major polyphenol in green tea. Recent studies have reported that EGCG can inhibit TRAIL-induced apoptosis and activate autophagic flux in cancer cells. However, the mechanism behind these processes is unclear.

Human prion protein-induced autophagy flux governs neuron cell damage in primary neuron cells.

An unusual molecular structure of the prion protein, PrPsc is found only in mammals with transmissible prion diseases. Prion protein stands for either the infectious pathogen itself or a main component of it. Recent studies suggest that autophagy is one of the major functions that keep cells alive and has a protective effect against the neurodegeneration.

Hinokitiol protects primary neuron cells against prion peptide-induced toxicity via autophagy flux regulated by hypoxia inducing factor-1.

Prion diseases are fatal neurodegenerative disorders that are derived from structural changes of the native PrPc. Recent studies indicated that hinokitiol induced autophagy known to major function that keeps cells alive under stressful conditions. We investigated whether hinokitiol induces autophagy and attenuates PrP (106-126)-induced neurotoxicity.

Activation of autophagy flux by metformin downregulates cellular FLICE-like inhibitory protein and enhances TRAIL- induced apoptosis.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily. TRAIL is regarded as one of the most promising anticancer agents, because it can destruct cancer cells without showing any toxicity to normal cells. Metformin is an anti-diabetic drug with anticancer activity by inhibiting tumor cell proliferation.

Melatonin protects skin keratinocyte from hydrogen peroxide-mediated cell death via the SIRT1 pathway.

Melatonin (N-acetyl-5-methoxytryptamine), which is primarily synthesized in and secreted from the pineal gland, plays a pivotal role in cell proliferation as well as in the regulation of cell metastasis and cell survival in a diverse range of cells. The aim of this study is to investigate protection effect of melatonin on H2O2-induced cell damage and the mechanisms of melatonin in human keratinocytes. Hydrogen peroxide dose-dependently induced cell damages in human keratinocytes and co-treatment of melatonin protected the keratinocytes against H2O2-induced cell damage.

Niacin alleviates TRAIL-mediated colon cancer cell death via autophagy flux activation.

Niacin, also known as vitamin B3 or nicotinamide is a water-soluble vitamin that is present in black beans and rice among other foods. Niacin is well known as an inhibitor of metastasis in human breast carcinoma cells but the effect of niacin treatment on TRAIL-mediated apoptosis is unknown. Here, we show that niacin plays an important role in the regulation of autophagic flux and protects tumor cells against TRAIL-mediated apoptosis.

Quercetin-induced autophagy flux enhances TRAIL-mediated tumor cell death.

Quercetin is a potent cancer therapeutic agent and dietary antioxidant present in fruit and vegetables. Quercetin prevents tumor proliferation by inducing cell cycle arrest and is a well known cancer therapeutic agent and autophagy mediator. We investigated whether quercetin enhances TRAIL-induced tumor cell death and the possible mechanism in human lung cancer cells.

EGCG-mediated autophagy flux has a neuroprotection effect via a class III histone deacetylase in primary neuron cells.

Prion diseases caused by aggregated misfolded prion protein (PrP) are transmissible neurodegenerative disorders that occur in both humans and animals. Epigallocatechin-3-gallate (EGCG) has preventive effects on prion disease; however, the mechanisms related to preventing prion diseases are unclear. We investigated whether EGCG, the main polyphenol in green tea, prevents neuron cell damage induced by the human prion protein.

Induction of cellular prion protein (PrPc) under hypoxia inhibits apoptosis caused by TRAIL treatment.

Hypoxia decreases cytotoxic responses to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein. Cellular prion protein (PrPc) is regulated by HIF-1α in neurons. We hypothesized that PrPc is involved in hypoxia-mediated resistance to TRAIL-induced apoptosis.

Deferoxamine inhibits TRAIL-mediated apoptosis via regulation of autophagy in human colon cancer cells.

Deferoxamine (DFO), an iron chelator, has numerous clinical applications for patients presenting with iron overload in regards to the improvement in the quality of life and overall survival. In addition, experimental iron chelators have demonstrated potent anticancer properties. The present study investigated the effects of DFO on TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in colon cancer cells and and the mechanism involved.