Role of Exogenous ATP in Modulating Inflammation in the Brain
REVIEW ARTICLE published: 01 September 2014 CELLULAR NEUROSCIENCE doi: 10.3389/fncel.2014.00260 The two-hit hypothesis for neuroinflammation: role of exogenous ATP in modulating inflammation in the brain Bernd L. Fiebich 1, Shamima Akter 2 and Ravi Shankar Akundi 2* 1 Department of Psychiatry and Psychotherapy, Neurochemistry Research Laboratory, University of Freiburg Medical School, Freiburg, Germany 2 Neuroinflammation Research Laboratory, Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, Delhi, India Edited by: Brain inflammation is a common occurrence following responses to varied insults such Rosanna Parlato, Ulm University, as bacterial infections, stroke, traumatic brain injury and neurodegenerative disorders. Germany A common mediator for these varied inflammatory responses is prostaglandin E2 Reviewed by: Hermona Soreq, The Hebrew (PGE2), produced by the enzymatic activity of cyclooxygenases (COX) 1 and 2. Previous University of Jerusalem, Israel attempts to reduce neuronal inflammation through COX inhibition, by use of nonsteroidal Mohamed Jaber, University of anti-inflammatory drugs (NSAIDs), have met with limited success. We are proposing the Poitiers, France two-hit model for neuronal injury—an initial localized inflammation mediated by PGE2 *Correspondence: (first hit) and the simultaneous release of adenosine triphosphate (ATP) by injured cells Ravi Shankar Akundi, Neuroinflammation Research (second hit), which significantly enhances the inflammatory response through increased Laboratory, Faculty of Life Sciences synthesis of PGE2. Several evidences on the role of exogenous ATP in inflammation have and Biotechnology, South Asian been reported, including contrary instances where extracellular ATP reduces inflammatory University, Akbar Bhawan, events. In this review, we will examine the current literature on the role of P2 receptors, Chanakyapuri, New Delhi—110021, Delhi, India to which ATP binds, in modulating inflammatory reactions during neurodegeneration.
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