P2X7 mediated phagocytosis of apoptotic cells: a common mechanism underlies neurological and eye disorders
Grant number: 1048082 | Funding period: 2013 - 2015
We have found a strong genetic linkage between a protein called P2X7 and a number of neurological disorders, in line with our recent discovery of a novel function of this protein in clearance of dying cells as removal of unhealthy neurons is essential to keep brain function promptly. Further study using genetic association, cell biology and animal models will lead to a conceptual advance on how neurological diseases are occurred and developed.
Related publications (16)
P2X7-mediated alteration of membrane fluidity is associated with the late stages of age-related macular degeneration.
Candace Drysdale, Keunha Park, Kirstan A Vessey, Xin Huang, Emily Caruso, Yihan Li, Joelyn Wong, James S Wiley, Erica Fletcher, Robyn H Guymer, Ben J Gu
We have shown deficits in monocyte phagocytosis from patients with age-related macular degeneration (AMD). Cell membrane fluidity ..
Leukocyte surface biomarkers implicate deficits of innate immunity in sporadic Alzheimer's disease
Xin Huang, Yihan Li, Christopher Fowler, James D Doecke, Yen Ying Lim, Candace Drysdale, Vicky Zhang, Keunha Park, Brett Trounson, Kelly Pertile, Rebecca Rumble, John W Pickering, Robert A Rissman, Floyd Sarsoza, Sara Abdel-Latif, Yong Lin, Vincent Dore, Victor Villemagne, Christopher C Rowe, Jurgen Fripp
INTRODUCTION: Blood-based diagnostics and prognostics in sporadic Alzheimer's disease (AD) are important for identifying at-risk i..
Identification of Leukocyte Surface P2X7 as a Biomarker Associated with Alzheimer's Disease
Yihan Li, Xin Huang, Christopher Fowler, Yen Y Lim, Simon M Laws, Noel Faux, James D Doecke, Brett Trounson, Kelly Pertile, Rebecca Rumble, Vincent Dore, Victor L Villemagne, Christopher C Rowe, James S Wiley, Paul Maruff, Colin L Masters, Ben J Gu
Alzheimer's disease (AD) has shown altered immune responses in the periphery. We studied P2X7 (a proinflammatory receptor and a sc..
Flow Cytometry Identifies an Early Stage of Platelet Apoptosis Produced by Agonists of the P2X1 and P2X7 Receptors
Joelyn Wong, Ben J Gu, Harry Teoh, Malgorzata Krupa, Mastura Monif, Mark Slee, James S Wiley
Platelets express P2X1 receptors and our data also show the expression of P2X7 receptors. We studied the role of both receptors in..
Deficits in Monocyte Function in Age Related Macular Degeneration: A Novel Systemic Change Associated With the Disease
Ben J Gu, Xin Huang, Pavan K Avula, Emily Caruso, Candace Drysdale, Kirstan A Vessey, Amber Ou, Christopher Fowler, Tian-Hua Liu, Yong Lin, Adam Horton, Colin L Masters, James S Wiley, Robyn H Guymer, Erica L Fletcher
Age-related macular degeneration (AMD) is characterized by the accumulation of debris in the posterior eye. In this study we evalu..
Real-time Live-cell Flow Cytometry to Investigate Calcium Influx, Pore Formation, and Phagocytosis by P2X7 Receptors in Adult Neural Progenitor Cells
Hannah C Leeson, Tailoi Chan-Ling, Michael D Lovelace, Jeremy D Brownlie, Michael W Weible, Ben J Gu
Live-cell flow cytometry is increasingly used among cell biologists to quantify biological processes in a living cell culture. Thi..
P2X7 Receptors Regulate Phagocytosis and Proliferation in Adult Hippocampal and SVZ Neural Progenitor Cells: Implications for Inflammation in Neurogenesis
Hannah C Leeson, Maria A Kasherman, Tailoi Chan-Ling, Michael D Lovelace, Jeremy C Brownlie, Kelly M Toppinen, Ben J Gu, Michael W Weible
Identifying the signaling mechanisms that regulate adult neurogenesis is essential to understanding how the brain may respond to n..
The scavenger activity of the human P2X7 receptor differs from P2X7 pore function by insensitivity to antagonists, genetic variation and sodium concentration: Relevance to inflammatory brain diseases
Amber Ou, Ben J Gu, James S Wiley
Activation of P2X7 receptors is widely recognised to initiate proinflammatory responses. However P2X7 also has a dual function as ..
Purinergic receptors P2RX4 and P2RX7 in familial multiple sclerosis
A Dessa Sadovnick, Ben J Gu, Anthony L Traboulsee, Cecily Q Bernales, Mary Encarnacion, Irene M Yee, Maria G Criscuoli, Xin Huang, Amber Ou, Carol J Milligan, Steven Petrou, James S Wiley, Carles Vilarino-Guell
Genetic variants in the purinergic receptors P2RX4 and P2RX7 have been shown to affect susceptibility to multiple sclerosis (MS). ..
Innate phagocytosis by peripheral blood monocytes is altered in Alzheimer's disease
Ben J Gu, Xin Huang, Amber Ou, Alan Rembach, Christopher Fowler, Pavan K Avula, Adam Horton, James D Doecke, Victor L Villemagne, S Lance Macaulay, Paul Maruff, Erica L Fletcher, Robyn Guymer, James S Wiley, Colin L Masters
Sporadic Alzheimer's disease (AD) is characterised by the deposition and accumulation of specific protein aggregates. Failure of c..
A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis
Ben J Gu, Judith Field, Sebastien Dutertre, Amber Ou, Trevor J Kilpatrick, Jeannette Lechner-Scott, Rodney Scott, Rodney Lea, Bruce V Taylor, Jim Stankovich, Helmut Butzkueven, Melissa Gresle, Simon M Laws, Steven Petrou, Sabine Hoffjan, Denis A Akkad, Colin A Graham, Stanley Hawkins, Anna Glaser, Sahl Khalid Bedri
Multiple sclerosis (MS) is a chronic relapsing-remitting inflammatory disease of the central nervous system characterized by oligo..
P2X7 Receptors Mediate Innate Phagocytosis by Human Neural Precursor Cells and Neuroblasts
Michael D Lovelace, Ben J Gu, Steven S Eamegdool, Michael W Weible, James S Wiley, David G Allen, Tailoi Chan-Ling
During early human neurogenesis there is overproduction of neuroblasts and neurons accompanied by widespread programmed cell death..
A Quantitative Method for Measuring Innate Phagocytosis by Human Monocytes Using Real-Time Flow Cytometry
Ben J Gu, Chun Sun, Stephen Fuller, Kristen K Skarratt, Steven Petrou, James S Wiley
Phagocytosis is central to immunity however a rapid and standardized method is much needed for quantitative assessment of the phag..
A rare functional haplotype of the P2RX4 and P2RX7 genes leads to loss of innate phagocytosis and confers increased risk of age-related macular degeneration
Ben J Gu, Paul N Baird, Kirstan A Vessey, Kristen K Skarratt, Erica L Fletcher, Stephen J Fuller, Andrea J Richardson, Robyn H Guymer, James S Wiley
Age-related macular degeneration (AMD) is a leading cause of blindness in Western countries and is diagnosed by the clinical appea..