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Therapeutic treatment of AICAR for Microglial inflammation in Alz | 48285

Journal of Neurology & Neurophysiology

ISSN - 2155-9562

Therapeutic treatment of AICAR for Microglial inflammation in Alzheimer’s disease

3rd International Conference and Exhibition on Neurology & Therapeutics

September 08-10, 2014 Hilton Philadelphia Airport, USA

Ayasolla K R, Jothika Challapalle, Shailendra Giri Singhal and Rahimipour S

Accepted Abstracts: J Neurol Neurophysiol

Abstract :

Introduction:Pro-inflammatory cytokines have been detected in AD brain and seem to play a role in the pathogenesis of AD. Our earlier reports investigated glial cell responses to LPS and Abeta, by upregulating the expression of cytokines TNF- α , IL-1 β , and IL-6, as well iNOS and COX-2. The present study was undertaken to investigate the therapeutic benefits of AICAR (a potent activator of AMP-activated protein kinase) in blocking the pro-oxidant/pro-inflammatory responses in microglia. Objectives: Our main objectives were a) to understand activation as well release of cytokines from activated microglia in response to accumulated A β , and therapeutic benefits of AICAR. Experimental methods: BV-2 microglia were used in these studies to understand LPS/ SMase/A β stimulated signaling mechanisms of NF κ B pathway leading to the release of NO, ROS generation, release of inflammatory cytokine (TNF- α , IL-1 β , IL-6) as well the scavenging macrophage like phagocytic functions of microglia. Results: AICAR inhibits LPS, and Smase activated cytokine release and NO production. AICAR also seem to promote A β phagocytosis. Further we observed a reduction in the stress signaling with a significant lowering in p-ERK, p-p38, p-Akt (ser 473) as well significant reduction of proteins such as p-NIK, p-IKK a/b and in p-p65 translocation. Conclusions: Microglia plays an active role in triggering the immune cytokine responses in the neuro-inflammatory process of AD. Hence AICAR treatment is effective in blocking cytokine release by possibly regulating NF κ B pathways.

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