From Analysis of Ischemic Mouse Brain Proteome to Identification of Human Serum Clusterin as a Potential Biomarker for Severity of Acute Ischemic Stroke.

Ischemic stroke is a devastating neurological disease that can cause permanent brain damage, but to date, few biomarkers are available to reliably assess the severity of injury during acute onset. In this study, quantitative proteomic analysis of ischemic mouse brain detected the increase in expression levels of clusterin (CLU) and cystatin C (CST3). Since CLU is a secretary protein, serum samples (n = 70) were obtained from acute ischemic stroke (AIS) patients within 24 h of stroke onset and together with 70 matched health controls.

Botanical Polyphenols Mitigate Microglial Activation and Microglia-Induced Neurotoxicity: Role of Cytosolic Phospholipase A2.

Microglia play a significant role in the generation and propagation of oxidative/nitrosative stress, and are the basis of neuroinflammatory responses in the central nervous system. Upon stimulation by endotoxins such as lipopolysaccharides (LPS), these cells release pro-inflammatory factors which can exert harmful effects on surrounding neurons, leading to secondary neuronal damage and cell death. Our previous studies demonstrated the effects of botanical polyphenols to mitigate inflammatory responses induced by LPS, and highlighted an important role for cytosolic phospholipase A2 (cPLA2) upstream of the pro-inflammatory pathways (Chuang et al.

Cytosolic phospholipase A2 plays a crucial role in ROS/NO signaling during microglial activation through the lipoxygenase pathway.

Background: Oxidative stress and inflammation are important factors contributing to the pathophysiology of numerous neurological disorders, including Alzheimer's disease, Parkinson's disease, acute stroke, and infections of the brain. There is well-established evidence that proinflammatory cytokines and glutamate, as well as reactive oxygen species (ROS) and nitric oxide (NO), are produced upon microglia activation, and these are important factors contributing to inflammatory responses and cytotoxic damage to surrounding neurons and neighboring cells. Microglial cells express relatively high levels of cytosolic phospholipase A2 (cPLA2), an enzyme known to regulate membrane phospholipid homeostasis and release of arachidonic acid (AA) for synthesis of eicosanoids.

Quercetin Attenuates Inflammatory Responses in BV-2 Microglial Cells: Role of MAPKs on the Nrf2 Pathway and Induction of Heme Oxygenase-1.

A large group of flavonoids found in fruits and vegetables have been suggested to elicit health benefits due mainly to their anti-oxidative and anti-inflammatory properties. Recent studies with immune cells have demonstrated inhibition of these inflammatory responses through down-regulation of the pro-inflammatory pathway involving NF-κB and up-regulation of the anti-oxidative pathway involving Nrf2. In the present study, the murine BV-2 microglial cells were used to compare anti-inflammatory activity of quercetin and cyanidin, two flavonoids differing by their alpha, beta keto carbonyl group.

Inhibition of microglial activation by elderberry extracts and its phenolic components.

Aims: Elderberry (Sambucus spp.) is one of the oldest medicinal plants noted for its cardiovascular, anti-inflammatory, and immune-stimulatory properties. In this study, we investigated the anti-inflammatory and anti-oxidant effects of the American elderberry (Sambucus nigra subsp.

Dietary Sutherlandia and elderberry mitigate cerebral ischemia-induced neuronal damage and attenuate p47phox and phospho-ERK1/2 expression in microglial cells.

Sutherlandia (Sutherlandia frutescens) and elderberry (Sambucus spp.) are used to promote health and for treatment of a number of ailments. Although studies with cultured cells have demonstrated antioxidative and anti-inflammatory properties of these botanicals, little is known about their ability to mitigate brain injury.

Sutherlandia frutescens ethanol extracts inhibit oxidative stress and inflammatory responses in neurons and microglial cells.

Sutherlandia frutescens (L.) R.Br.

Role of cytosolic phospholipase A2 in oxidative and inflammatory signaling pathways in different cell types in the central nervous system.

Phospholipases A(2) (PLA(2)s) are important enzymes for the metabolism of fatty acids in membrane phospholipids. Among the three major classes of PLA(2)s in the mammalian system, the group IV calcium-dependent cytosolic PLA(2) alpha (cPLA(2)α) has received the most attention because it is widely expressed in nearly all mammalian cells and its active participation in cell metabolism. Besides Ca(2+) binding to its C2 domain, this enzyme can undergo a number of cell-specific post-translational modifications, including phosphorylation by protein kinases, S-nitrosylation through interaction with nitric oxide (NO), as well as interaction with other proteins and lipid molecules.

Magnolia polyphenols attenuate oxidative and inflammatory responses in neurons and microglial cells.

Background: The bark of magnolia has been used in Oriental medicine to treat a variety of remedies, including some neurological disorders. Magnolol (Mag) and honokiol (Hon) are isomers of polyphenolic compounds from the bark of Magnolia officinalis, and have been identified as major active components exhibiting anti-oxidative, anti-inflammatory, and neuroprotective effects. In this study, we investigate the ability of these isomers to suppress oxidative stress in neurons stimulated by the ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA) and oxidative and inflammatory responses in microglial cells activated by interferon-γ (IFNγ) and lipopolysaccharide (LPS).

Integrating cytosolic phospholipase A₂ with oxidative/nitrosative signaling pathways in neurons: a novel therapeutic strategy for AD.

The pathophysiology of Alzheimer's disease (AD) is comprised of complex metabolic abnormalities in different cell types in the brain. To date, there are not yet effective drugs that can completely inhibit the pathophysiological event, and efforts have been devoted to prevent or minimize the progression of this disease. Much attention has focused on studies to understand aberrant functions of the ionotropic glutamate receptors, perturbation of calcium homeostasis, and toxic effects of oligomeric amyloid beta peptides (Aβ) which results in production of reactive oxygen and nitrogen species and signaling pathways, leading to mitochondrial dysfunction and synaptic impairments.

Distinct roles for Arp2/3 regulators in actin assembly and endocytosis.

The Arp2/3 complex is essential for actin assembly and motility in many cell processes, and a large number of proteins have been found to bind and regulate it in vitro. A critical challenge is to understand the actions of these proteins in cells, especially in settings where multiple regulators are present. In a systematic study of the sequential multicomponent actin assembly processes that accompany endocytosis in yeast, we examined and compared the roles of WASp, two type-I myosins, and two other Arp2/3 activators, along with that of coronin, which is a proposed inhibitor of Arp2/3.