Mitoxantrone Represses Markers of Microglial Activation and Inflammation

Multiple sclerosis (MS) is a neurodegenerative disease characterized by an autoimmune attack against myelin sheaths in the central nervous system (CNS). Resulting debilitations vary from sensory, motor, and coordination abnormalities to visual difficulties as well as bowel, bladder, sexual, and cognitive dysfunction (Fox, 2006). Mitoxantrone (Novantrone) is an FDAapproved drug used to treat the secondary-progressive form ofMS due to its demonstrated immunosuppressive properties. While the mechanism of action of mitoxantrone is not yet well understood, and is limited in its use due to cardiotoxicity, the aim of this study was to determine the effect of mitoxantrone on microglial and astrocyte activation as a measure of the inflammatory response. Enzyme-linked immunosorbent assays (ELISA) showed that lipopolysaccharide (LPS) stimulates markers of activation including nitric oxide (NO), interleukin-1-beta (IL-l b), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in N9 cultured microglia, and moreover, that mitoxantrone inhibits these effects in a dosedependent manner

Resveratrol Effects on Astrocyte Function: Relevance to Neurodegenerative Diseases

Inflammatory molecules have been implicated in the pathogenesis of neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis. Resveratrol is an antifungal compound found in the skins of red grapes and other fruits and nuts. We examined the ability of resveratrol to inhibit lipopolysaccharide (LPS)-induced production of inflammatory molecules from primary mouse astrocytes. Resveratrol inhibited LPS-induced production of nitric oxide (NO); the cytokines tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1β), and IL-6; and the chemokine monocyte chemotactic protein-1 (MCP-1), which play critical roles in innate immunity, by astrocytes. Resveratrol also suppressed astrocyte production of IL-12p40 and IL-23, which are known to alter the phenotype of T cells involved in adaptive immunity. Finally resveratrol inhibited astrocyte production of C-reactive protein (CRP), which plays a role in a variety of chronic inflammatory disorders. Collectively, these studies suggest that resveratrol may be an effective therapeutic agent in neurodegenerative diseases initiated or maintained by inflammatory processes

Muscle p70S6K phosphorylation in response to soy and dairy rich meals in middle aged men with metabolic syndrome: a randomised crossover trial

The mammalian target of rapamycin (mTOR) pathway is the primary regulator of muscle protein synthesis. Metabolic syndrome (MetS) is characterized by central obesity and insulin resistance; little is known about how MetS affects the sensitivity of the mTOR pathway to feeding