Selective brain penetrable Nurr1 transactivator for treating Parkinson's disease

• DOI: 10.18632/oncotarget.7191
• Publication Date: 2016-02-05T01:13:08Z
• Authors: Jun Wang; Weina Bi; Wei Zhao; Merina Varghese; Rick J. Koch; Ruth H. Walker; Roshantha A. Chan...; Martin E. Sanders; Amanda Janesick; Bruce Blumberg; Libby Ward; Lap Ho; Giulio M. Pasinetti
• Keywords: Retinoid X receptor

// Jun Wang 1,2 , Weina Bi 1 Wei Zhao Merina Varghese Rick J. Koch 3 Ruth H. Walker Roshantha A. Chandraratna 4 Martin E. Sanders Amanda Janesick 5 Bruce Blumberg Libby Ward Lap Ho and Giulio M. Pasinetti Department of Neurology, Icahn School Medicine at Mount Sinai, New York, NY, USA 2 Geriatric Research, Education Clinical Center, Bronx, James Peters Veterans Affairs Medical Io Therapeutics Inc., Santa Ana, CA, Departments Developmental Cell Biology, Pharmaceutical Sciences, University California, Irvine, Correspondence to: Pasinetti, email: Keywords : brain bioavailable, dopaminergic, nuclear receptor related-1 protein, Parkinson's disease, retinoid X receptor, Gerotarget Received September 23, 2015 Accepted January 2016 Published February 04, Abstract disease (PD) is one the most common movement disorders, currently there no effective treatment that can slow progression. Preserving enhancing DA neuron survival increasingly regarded as promising therapeutic strategy for treating PD. IRX4204 a second generation (RXR) agonist has cross reactivity with retinoic acid receptors, farnesoid liver receptors or peroxisome proliferator-activated PPARγ. We found promotes maintenance nigral dopaminergic (DA) neurons in dose-dependent manner primary mesencephalic cultures. Brain bioavailability studies demonstrate blood barrier reach nM concentration. Oral administration activate Nurr1 downstream signaling substantia nigra (SN) andattenuate neurochemical motor deficits rat model Our study suggests represents novel, potent selective pharmacological means to cellular RXR-Nurr1 promote SN PD prevention and/or treatment.