Artemisinin alleviates astrocyte overactivation and neuroinflammation by modulating the IRE1/NF-κB signaling pathway in in vitro and in vivo Alzheimer's disease models.

Recent studies have shown that neuroinflammation and heightened glial activity, particularly astrocyte overactivation, are associated with Alzheimer's disease (AD). Abnormal accumulation of amyloid-beta (Aβ) induces endoplasmic reticulum (ER) stress and activates astrocytes. Artemisinin (ART), a frontline anti-malarial drug, has been found to have neuroprotective properties.

Anti-Inflammatory Effects of Clarstatin, a Shared-Epitope-Antagonistic Cyclic Peptide, on Experimental Autoimmune Uveitis in Mice.

Purpose: Polymorphism and mutations of human leukocyte antigens (HLAs) and calreticulin are risk factors for uveitis. Here, we sought to determine the therapeutic effects of Clarstatin, a cyclic peptide antagonist of the HLA shared-epitope-calreticulin interaction, in experimental autoimmune uveitis (EAU) models.

Methods: Mice were injected with Clarstatin intraperitoneally and its effect was compared to that of corticosteroid.

Artemisinin conferred cytoprotection to human retinal pigment epithelial cells exposed to amiodarone-induced oxidative insult by activating the CaMKK2/AMPK/Nrf2 pathway.

Background: Ocular toxicity is a severe adverse effect that limits the chronic clinical use of the antiarrhythmic drug amiodarone. Here, we aimed to evaluate the cytoprotective effect of artemisinin and explore the potential signalling pathways in human retinal pigment epithelial (RPE) cell cultures.

Methods: D407 cell cultures were exposed to amiodarone and the impact of artemisinin was evaluated.

Rasagiline Exerts Neuroprotection towards Oxygen-Glucose-Deprivation/Reoxygenation-Induced GAPDH-Mediated Cell Death by Activating Akt/Nrf2 Signaling.

Rasagiline (Azilect) is a selective monoamine oxidase B (MAO-B) inhibitor that provides symptomatic benefits in Parkinson's disease (PD) treatment and has been found to exert preclinical neuroprotective effects. Here, we investigated the neuroprotective signaling pathways of acute rasagiline treatment for 22 h in PC12 neuronal cultures exposed to oxygen-glucose deprivation (OGD) for 4 h, followed by 18 h of reoxygenation (R), causing 40% aponecrotic cell death. In this study, 3-10 µM rasagiline induced dose-dependent neuroprotection of 20-80%, reduced the production of the neurotoxic reactive oxygen species by 15%, and reduced the nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by 75-90%.

Development of Clarstatin, a Novel Drug Lead for the Therapy of Autoimmune Uveitis.

We describe the design, synthesis, and activity of a potent thiourea-bridged backbone cyclic peptidomimetic known as Clarstatin, comprising a 5-amino acid sequence (Q/D)-(R/K)-X-X-A-(Gln/Asp)-(Arg/Lys)-AA-AA-Ala-based on a motif called "shared epitope (SE)", specifically present in specific alleles of the gene. This SE binds to a particular site within the proline reach domain (P-domain) of the cell surface-calreticulin (CS-CRT). CS-CRT is a multifunctional endoplasmic reticulum (ER) calcium-binding protein that is located on the cell surface of T cells and triggers innate immune signaling, leading to the development of inflammatory autoimmune diseases.