Alzheimer’s breakthrough: Coverage by SF Gate and Healthline on “Prostaglandin signaling suppresses beneficial microglial function in Alzheimer’s disease models.”
Drug Combination helps control type 1 diabetes: Coverage by US News on “Anti-thymocyte globulin/G-CSF treatment preserves β cell function in patients with established type 1 diabetes.”
Possible new stent to prevent heart attacks: Coverage by EIN News on “Oxido-reductive regulation of vascular remodeling by receptor tyrosine kinase ROS1.”
Autoimmunity linked to unstable proteins: Coverage by Asian Scientist Magazine on “Cell-surface MHC density profiling reveals instability of autoimmunity-associated HLA.”
Porcine model of cardiac sodium channelopathy: Coverage by MedicalResearch.com on “Genetically engineered SCN5A mutant pig hearts exhibit conduction defects and arrhythmias.”
Microglia, the innate immune cells of the CNS, perform critical inflammatory and noninflammatory functions that maintain normal neural function. For example, microglia clear misfolded proteins, elaborate trophic factors, and regulate and terminate toxic inflammation. In Alzheimer’s disease (AD), however, beneficial microglial functions become impaired, accelerating synaptic and neuronal loss. Better understanding of the molecular mechanisms that contribute to microglial dysfunction is an important objective for identifying potential strategies to delay progression to AD. The inflammatory cyclooxygenase/prostaglandin E2 (COX/PGE2) pathway has been implicated in preclinical AD development, both in human epidemiology studies and in transgenic rodent models of AD. Here, we evaluated murine models that recapitulate microglial responses to Aβ peptides and determined that microglia-specific deletion of the gene encoding the PGE2 receptor EP2 restores microglial chemotaxis and Aβ clearance, suppresses toxic inflammation, increases cytoprotective insulin-like growth factor 1 (IGF1) signaling, and prevents synaptic injury and memory deficits. Our findings indicate that EP2 signaling suppresses beneficial microglia functions that falter during AD development and suggest that inhibition of the COX/PGE2/EP2 immune pathway has potential as a strategy to restore healthy microglial function and prevent progression to AD.
Jenny U. Johansson, Nathaniel S. Woodling, Qian Wang, Maharshi Panchal, Xibin Liang, Angel Trueba-Saiz, Holden D. Brown, Siddhita D. Mhatre, Taylor Loui, Katrin I. Andreasson
Michael J. Haller, Stephen E. Gitelman, Peter A. Gottlieb, Aaron W. Michels, Stephen M. Rosenthal, Jonathan J. Shuster, Baiming Zou, Todd M. Brusko, Maigan A. Hulme, Clive H. Wasserfall, Clayton E. Mathews, Mark A. Atkinson, Desmond A. Schatz
Angioplasty and stenting is the primary treatment for flow-limiting atherosclerosis; however, this strategy is limited by pathological vascular remodeling. Using a systems approach, we identified a role for the network hub gene glutathione peroxidase-1 (
Ziad A. Ali, Vinicio de Jesus Perez, Ke Yuan, Mark Orcholski, Stephen Pan, Wei Qi, Gaurav Chopra, Christopher Adams, Yoko Kojima, Nicholas J. Leeper, Xiumei Qu, Kathia Zaleta-Rivera, Kimihiko Kato, Yoshiji Yamada, Mitsutoshi Oguri, Allan Kuchinsky, Stanley L. Hazen, J. Wouter Jukema, Santhi K. Ganesh, Elizabeth G. Nabel, Keith Channon, Martin B. Leon, Alain Charest, Thomas Quertermous, Euan A. Ashley
Polymorphisms within
Hiroko Miyadera, Jun Ohashi, Åke Lernmark, Toshio Kitamura, Katsushi Tokunaga
David S. Park, Marina Cerrone, Gregory Morley, Carolina Vasquez, Steven Fowler, Nian Liu, Scott A. Bernstein, Fang-Yu Liu, Jie Zhang, Christopher S. Rogers, Silvia G. Priori, Larry A. Chinitz, Glenn I. Fishman