RAGE-A? Complexes Play A Crucial Role In Triggering Inflammatory, Autoimmune Related Cascade Of Cyclic Events Leading To AD-pathogenesis | 12556
Journal of Alzheimers Disease & Parkinsonism
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Alzheimer?s disease (AD) is a progressive neurodegenerative disorder that gradually destroys a person?s Memory& cognition.
Research efforts derived from our lab from past ten years along with others across the globe, strongly suggests that: amyloid
beta (A?) and the receptor for advanced glycation end products (RAGE) play a crucial role in AD pathogenesis. RAGE, facilitates
the translocation of A? from the periphery into the brain, mediates A?-induced neurotoxicity, and enhances the release of proinflammatory
cytokines triggering an inflammatory response. It has been shown that AGEs also regulate RAGE gene expression
in blood vessels, and that the AGE-RAGE interaction enables a sustained and upwardly spiraling inflammatory component
preventing the completion of normal tissue repair mechanisms. A? also binds with ?7 subtype of the nicotinic acetylcholine
receptor (?7nAChR) which are crucial for memory and cognitive functions of the brain ( Mruthinti et al.,2006). RAGE-A?
complexes are more immunogenic compared to either RAGE or A? and their long-term presence potentiates A? aggregation,
oxidative stress, inflammation, vascular dysfunction, and autoimmunity. We prepared a simple and safe water-based oral vaccine
for AD, incorporating an in-vitro prepared RAGE-A? complex antigen. Our data clearly suggested that, RAGE-A? immunogen
induced: a) significantly higher antibody IgG serum titers and b) improved their cognitive test scores in AD-Tg mice and Primates;
compared to either A? or RAGE alone (Webster et al., 2012). We conclude that, an oral vaccine therapy using water based RAGEA?
complex immunogen may be more effective treatment for AD than vaccination with A? or RAGE alone.
Shyamala Mruthinti received B.Sc., M.A., M.S. and Ph.D. from Osmania and M. S. University of Baroda, India. She was hired as a Post-Doctoral
Fellow & as an Assistant Professor in the Department of Immunology, Medical College of GA from 1987-1996. She joined Veterans Medical
Administration in 1996 as Research Pharmacologist and received Career Development award and Merit Review award as Principle Investigator
from 2000-2010 on AD research. She has 6 grants, 25 publications. She received ?Outstanding-Performance & Research- Excellence-Awards? in
2010 from VA. She is the founding member of Immuno-Rx & currently CEO of Datta ImmunoChem. Inc.
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