Inflammation and oxidative stress are thought to play determinant roles in the pathogenesis of amyotrophic lateral sclerosis (ALS). Degenerating motor neurons produce signals that activate microglia to release reactive oxygen species (ROS) and proinflammatory cytokines, resulting in a vicious cycle of neurodegeneration. The ALS-causing mutant protein Cu(+)/Zn(+) superoxide dismutase SOD1-G93A d...

The ATP-gated P2X7 ion channel is an abundant microglial protein in the CNS that plays an important pathological role in executing ATP-driven danger signal transduction. Emerging data has generated scientific interest and excitement around targeting the P2X7 ion channel as a potential drug target for CNS disorders. Over the past years, a wealth of data has been published on CNS P2X7 biology, in...

Activation of the purinergic P2X7 receptor by extracellular ATP induces the shedding of cell-surface molecules including the low-affinity IgE receptor, CD23 from leukocytes. CD23 is a known substrate of a disintegrin and metalloprotease (ADAM)10. The aim of the current study was to determine if P2X7 activation induced the shedding of the chemokine CXCL16, an ADAM10 substrate. Using immunolabell...

The P2X7 purinergic receptor is a ligand-gated cation channel expressed on leukocytes including microglia. This study aimed to determine if P2X7 activation induces the uptake of organic cations, reactive oxygen species (ROS) formation, and death in the murine microglial EOC13 cell line. Using the murine macrophage J774 cell line as a positive control, RT-PCR, immunoblotting, and immunolabelling...

The brain distribution and functional role of glial P2X7 receptors are broader and more complex than initially anticipated. We characterized P2X7 receptors from cerebellar astrocytes at the molecular, immunocytochemical, biophysical, and cell physiologic levels. Mouse cerebellar astrocytes in culture express mRNA coding for P2X7 receptors, which is translated into P2X7 receptor protein as prove...

P2x7 receptors are Purineric receptors that are extracellular ATP-gated ion channel. These receptors require high dose or prolonged exposure to ATP for initial activation. The Activation of these receptors facilitates the formation of inflammasome which activates caspase 1. The P20 and P10 subunits of caspase 1 form active enzyme that then releases active interleukin (IL)-1 β and IL-18, tu...

Controlled ATP release has been demonstrated from many neuronal and non-neuronal cell types. Once released, extracellular ATP acts on cells in a paracrine manner via purinergic receptors. Considerable evidence now suggests that extracellular nucleotides, signaling via P2 receptors, play important roles in bone homeostasis modulating both osteoblast and osteoclast function. In this study, we dem...