Scholars International

Neuroscience and Brain Disorders Forum

THEME: "Emerging Perspectives in Neurology and Brain Research"

img2 23-24 May 2022
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Emily L Ward

Emily L Ward

University of London, UK

Jasmonic acid and methyl jasmonate attenuate cAMP-driven neuroinflammation via crosstalk with the prostaglandin E2/receptor EP2 signaling axis

Biography

Emily Ward aims to pursue a PhD using methods of cellular and molecular biology to explore the mechanisms that underlie neurological disorders, including neurodegenerative diseases. She completed an independent master’s research project that assessed the mechanisms by which neuroinflammation is initiated and sustained. Following her recent graduation from her master’s program, she began working as a medical writer for a communications agency that specializes in representing clients companies with focus in oncology and rare diseases. Emily hopes to contribute to the elusive field of neuroscience and to continue to collaborate with institutions that have a focus on brain sciences.

Abstract

The jasmonates are a class of oxylipin phytohormones known to exhibit anti-inflammatory, antioxidant, and anti-cancer effects in mammalian cells. We investigated the ability of three jasmonate compounds (jasmonic acid, methyl jasmonate, and 12-OPDA) and two structurally distinct jasmonate precursors (alpha-linolenic acid and palmitic acid) to attenuate inflammation in an in vitro model of neurodegenerative disease, for which the mechanisms of action have not been well identified. The study modeled chronic neuroinflammation in SH-SY5Y neuroblastoma cells using exogenous prostaglandin E2 (PGE2) treatment. Prostaglandin E2 caused concentration-dependent levels of inflammation and cell death, which were attenuated by the jasmonates. To this end, structural similarities between the jasmonates and PGE2 were correlated with increased potency of their

anti-inflammatory effects. Downstream biomarkers of signaling through the pro-inflammatory E prostanoid receptor subtype 2 (EP2) were then quantified using immunohistochemistry assay to investigate whether the attenuation was correlated with crosstalk to PGE2/receptor EP2 signaling. Of the compounds tested, the two most structurally similar to PGE2, jasmonic acid (JA) and methyl jasmonate (MeJA), decreased pro-inflammatory cAMP signaling through the PGE2/ receptor EP2 pathway. We created structural models and molecular binding simulations that serve as evidence for our hypothesis that JA and MeJA achieve this crosstalk through competitive inhibition of the receptor EP2. This novel finding has implications in the study of neurodegenerative diseases for which the disease pathology is related to chronic neuroinflammation, including Alzheimer’s Disease, Parkinson’s Disease, amyotrophic lateral sclerosis and multiple sclerosis. In addition, these findings add to the understanding of the relationship between pro-inflammatory prostaglandin E2 signaling and chronic inflammation.