Receptor for AGE (RAGE) Signal Transduction in Amyotrophic Lateral Sclerosis: In Vivo Imaging and Novel Therapeutic Approaches
Technical Report,01 Jul 2018,30 Jun 2019
New York University School of Medicine New York United States
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We hypothesized that the receptor for advanced glycation end products RAGE is implicated in the pathogenesis of ALS, at least in part through microglial perturbation. Our findings 1 RAGE-positive Cd11b-positive cells are increased in the ventral horn of male and femaleSOD1G93A mouse lumbar spinal cord and male wild-type mice displayed higher proportions of RAGE-positive Cd11b cells than female wild-type mice. 2 In combined male and female SOD1G93A mice, microglia deletion of Ager in the ALS mouse background prolongs survival and slows loss of body weight and motor function. We identified an independent negative effect of the Cre recombinase mousseline in the ALS background Cx3cr1ERT2 cre. At this time, we are finalizing all mouse groups male and female so that ample power is achieved for each line in order to finalize conclusions. 3 PET imaging using tracers to mark inflammation suggests higher spinal cord inflammation at day 100 and day 130 of life in SOD1G93A mice vs. controls. 4 Orally available medicated chow small molecule antagonists of RAGEDIAPH1 are being tested in SOD1G93A mice. Collectively, our data suggest deleterious roles for RAGE in ALS and indicate that further testing of this concept is warranted in this disease.
- Anatomy and Physiology
- Medicine and Medical Research