Inhibition of iron-induced cofilin activation and inflammation in microglia by a novel cofilin inhibitor.

Neuroinflammatory conditions linked to iron dysregulation pose significant challenges in neurodegenerative diseases. Iron-loaded microglia are observed in the brains of patients with various neuroinflammatory conditions, yet how iron overload affects microglial function and contributes to various neuroinflammatory processes is poorly understood. This in vitro study elucidates the relationship between excess iron, cofilin activation, and microglial function, shedding light on potential therapeutic avenues.

Neuroprotection or Sex Bias: A Protective Response to Traumatic Brain Injury in the Females.

Traumatic brain injury (TBI) is a major healthcare problem and a common cause of mortality and morbidity. Clinical and preclinical research suggests sex-related differences in short- and longterm outcomes following TBI; however, males have been the main focus of TBI research. Females show a protective response against TBI.

The ER chaperone, BIP protects Microglia from ER stress-mediated Apoptosis in Hyperglycemia.

A major endoplasmic reticulum (ER) chaperone, binding of Immunoglobulin heavy chain protein (BIP) facilitates the assembly of newly synthesized proteins in the ER. Microglia vigorously respond to brain injuries and eliminate the damaged neuronal and apoptotic cells through phagocytosis in the central nervous system. However, the mechanism of BIP-mediated microglial function is not clear in hyperglycemia.

Cofilin Inhibitor Protects against Traumatic Brain Injury-Induced Oxidative Stress and Neuroinflammation.

Microglial activation and failure of the antioxidant defense mechanisms are major hallmarks in different brain injuries, particularly traumatic brain injury (TBI). Cofilin is a cytoskeleton-associated protein involved in actin binding and severing. In our previous studies, we identified the putative role of cofilin in mediating microglial activation and apoptosis in ischemic and hemorrhagic conditions.

Impairment of RPN4, a transcription factor, induces ER stress and lipid abnormality in Saccharomyces cerevisiae.

Accumulation of misfolded/unfolded proteins in the endoplasmic reticulum (ER) induces ER stress. The transcription factor RPN4 {"Regulatory Particle Non-ATPase"} regulates protein homeostasis by degrading proteins that elude proper folding or assembly via the proteasomal degradation pathway. Here, we studied the lipid alterations exerted by Saccharomyces cerevisiae to mitigate (ER) stress during adaptive responses in rpn4∆ cells.

Stroke: Molecular mechanisms and therapies: Update on recent developments.

Stroke, a neurological disease, is one of the leading causes of death worldwide, resulting in long-term disability in most survivors. Annual stroke costs in the United States alone were estimated at $46 billion recently. Stroke pathophysiology is complex, involving multiple causal factors, among which atherosclerosis, thrombus, and embolus are prevalent.

Synthesis and Pharmacological Evaluation of Novel Triazole-Pyrimidine Hybrids as Potential Neuroprotective and Anti-neuroinflammatory Agents.

Objective: Neuroprotection is a precise target for the treatment of neurodegenerative diseases, ischemic stroke, and traumatic brain injury. Pyrimidine and its derivatives have been proven to use antiviral, anticancer, antioxidant, and antimicrobial activity prompting us to study the neuroprotection and anti-inflammatory activity of the triazole-pyrimidine hybrid on human microglia and neuronal cell model.

Methods: A series of novel triazole-pyrimidine-based compounds were designed, synthesized and characterized by mass spectra, 1HNMR, 13CNMR, and a single X-Ray diffraction analysis.

First-in-Class Dual Mechanism Ferroptosis-HDAC Inhibitor Hybrids.

HDAC inhibitors are an attractive class of cytotoxic agents for the design of hybrid molecules. Several HDAC hybrids have emerged over the years, but none combines HDAC inhibition with ferroptosis, a combination which is being extensively studied because it leads to enhanced cytotoxicity and attenuated neuronal toxicity. We combined the pharmacophores of and molecules to design the first-in-class dual mechanism hybrid molecules, which induce ferroptosis and inhibit HDAC proteins.

ATP-binding cassette protein ABCA7 deficiency impairs sphingomyelin synthesis, cognitive discrimination, and synaptic plasticity in the entorhinal cortex.

Sphingomyelin (SM) is an abundant plasma membrane and plasma lipoprotein sphingolipid. We previously reported that ATP-binding cassette family A protein 1 (ABCA1) deficiency in humans and mice decreases plasma SM levels. However, overexpression, induction, downregulation, inhibition, and knockdown of ABCA1 in human hepatoma Huh7 cells did not decrease SM efflux.

IQGAP1 control of centrosome function defines distinct variants of triple negative breast cancer.

Triple negative breast cancer (TNBC) is a heterogenous and lethal disease that lacks diagnostic markers and therapeutic targets; as such common targets are highly sought after. IQGAP1 is a signaling scaffold implicated in TNBC, but its mechanism is unknown. Here we show that IQGAP1 localizes to the centrosome, interacts with and influences the expression level and localization of key centrosome proteins like BRCA1 and thereby impacts centrosome number.

Disruption in phosphate transport affects membrane lipid and lipid droplet homeostasis in Saccharomyces cerevisiae.

Phosphate plays a crucial role in phospholipid metabolism and it is transported by the phosphate (Pi) transporters. Phospholipids are building blocks of the cell membrane, and essential for cell growth; however, the role of phosphate transporters in lipid metabolism remains elusive. The present study shows that the deletion of Pi transporters exhibited an increase in both phospholipid and neutral lipid levels when compared to wild type.

Crosstalk between protein N-glycosylation and lipid metabolism in Saccharomyces cerevisiae.

The endoplasmic reticulum (ER) is a multi functional organelle and plays a crucial role in protein folding and lipid biosynthesis. The SEC59 gene encodes dolichol kinase, required for protein glycosylation in the ER. The mutation of sec59-1 caused a protein N-glycosylation defect mediated ER stress resulting in increased levels of phospholipid, neutral lipid and sterol, whereas growth was reduced.