Whilst significant advances have been made to identify the contribution of the cytotoxic agents released from microglia to the neurodegenerative process, it is less clear and remains to be determined which factors trigger microglial activation in these various disorders. In neurodegenerative selleck diseases such as Alzheimers, for example, players involved in the inflammatory process include S100a9, B amyloid peptides, macrophage colony Inhibitors,Modulators,Libraries stimulating factor and acute phase proteins such as C reactive protein, amyloid P and secreted phos pholipase Inhibitors,Modulators,Libraries A2 IIA, among others. Recent studies have revealed that S100a9, AB and macrophage colony stimulating factor themselves can promote the reactivity of microglia to enhance their Inhibitors,Modulators,Libraries neurotoxicity. However, any role that sPLA2 IIA might play in microglia activation is still unknown.

Secreted phospholipases A2 represent a family of eleven low molecular mass, calcium dependent lipolytic enzymes. They catalyze the hydrolysis of the sn 2 ester bond of glycerophospholipids present in cell membranes to form essential cell signaling Inhibitors,Modulators,Libraries molecules. They are widely distributed in human tissues including brain, where their specific function is still largely unclear, although current evidence suggests that sPLA2s may affect some neuronal functions, such as neuritogen esis, neurotoxicity, neurotransmitter release and survival. Different levels of sPLA2 activity have been found in various regions of the central nervous system in both humans and rodents, and the subtypes identified include sPLA2 IIA, IIC, IIE, II, V, X and XII.

Secreted Inhibitors,Modulators,Libraries PLA2 IIA was first identified in synovial fluid, and then characterized as an acute phase protein under the transcriptional control of pro inflammatory cytokine signaling. Later on, its presence in tears was reported and it came to be considered a powerful innate ocular surface barrier against Gram positive bacteria. Its serum levels dramatically increase under pathological conditions that involve systemic inflam matory processes such as sepsis, rheumatoid selleckchem Tipifarnib arthritis, and cardiovascular disease. Additionally, enhanced expression of sPLA2 IIA has also been found in certain neurological disorders and as a result of brain insult, it being associated with CNS injuries such as cerebral ischemia or mechanical damage to spinal cord tissue. Recent reports have shown it to be up regulated in both cerebrospinal fluid and brain of patients with Alzheimers disease. In fact, increased immunoreactiv ity for sPLA2 IIA has been reported in reactive astrocytes of the cortex and hippocampus around AB containing pla ques.