Neurological disorders are diseases that affect the brain, central and the autonomic nervous system. According to the University Of California San Francisco, there are more than 600 neurological disorders. Of the many neurological disorders, the most common neurodegenerative diseases among US population is Alzheimer's and Multiple sclerosis. The Multiple Sclerosis Foundation estimates that more than 400,000 people in the United States have Multiple Sclerosis, and about 5.5 million Americans live with Alzheimer's dementia. The pathogenesis of these neurodegenerative diseases has been attributed to inflammatory responses in the brain.
The process of the inflammatory response is the release of Pro-inflammatory cytokines, increased expression of endothelial adhesion and chemotactic factors and activation of brain immune effector cells. The brain immune cells, Microglia and Astrocytes are activated by a variety of stimuli. They produce inflammatory cytokines and chemokines that accelerate disease progression. The inflammatory chemokine of interest is Glial cells derived CCL2/MCP-1. It causes initiation and progression of inflammatory responses by promoting recruitment and migration of inflammatory cells. Hence interventions aimed at supporting the activity of CCL2/MCP-1 is the therapeutic strategy for the treatment of neurodegenerative diseases such as Multiple Sclerosis and Alzheimer's disease.
Peroxisome proliferator-activated receptors (PPARs) are ligand activated transcription factors. PPARs have been reported to be highly expressed in adipocytes, demonstrated to have important roles in adipocyte differentiation, lipid biosynthesis and glucose homeostasis. A subtype of PPAR, PPAR-γ has been reported to have anti-inflammatory effect on pro-inflammatory molecules. According to several studies PPAR-γactivators have shown promising beneficial effects on animal models of neurodegenerative diseases such as Multiple Sclerosis, Alzheimer's disease, Brain Ischemia.
ETYA or 5,8,11,14-Eicosatetraynoic Acid is one such PPAR-γ activator that has suggested therapeutic use in the treatment of neurodegenerative diseases. 5,8,11,14-Eicosatetraynoic Acid (ETYA), is an Arachidonic Acid analog. It is reported to inhibit up-regulation of pro-inflammatory genes. ETYA has an anti-inflammatory mechanism, by increasing HuR-mediated-MKP-1 mRNA stability that leads to the specific suppression of CCL2AMCP-1 during inflammatory processes. Studies have shown that ETYA increases MKP-1 expression through HuR at the post-transcriptional level in a receptor-independent manner. Thereby providing evidence that ETYA is a potential therapeutic modulator of inflammation.
ETYA's influence on suppressing CCL2/MCP-1 expression is an evidence that points to the fact that ETYA is an emerging therapeutic strategy for the treatment of debilitating neurodegenerative diseases such as Alzheimer, Multiple Sclerosis, and Brain Ischemia.
5, 8, 11, 14-eicosatetraynoic acid suppresses CCL2/MCP-1 expression in IFN-γ-stimulated astrocytes by increasing MAPK phosphatase-1 mRNA stability - Jee Hoon Lee, Hyunmi Kim, Joo Hong Woo, Eun-hye Jo and Ilo Jou
Incorporation of 5,8,11,14-eicosatetraynoic acid (ETYA) into cell lipids: competition with arachidonic acid for esterification - Taylor AS, Morrison AR, Russell JH.