Diab Asim, Hussain Rehana Z, Lovett-Racke Amy E, Chavis Janet A, Drew Paul D, Racke Michael K
Department of Neurology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9036, USA.
J Neuroimmunol. 2004 Mar;148(1-2):116-26. doi: 10.1016/j.jneuroim.2003.11.010.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear-receptor superfamily that binds to DNA with retinoid X receptors (RXRs) as PPAR-RXR heterodimers. In experimental autoimmune encephalomyelitis (EAE), the gene expression of PPAR-gamma was demonstrated in spinal cord during the course of EAE. Administration of 15-deoxy-(12,14)-prostaglandin J2 (15d-PGJ2) or 9-cis-retinoic acid (RA) alone at the onset of clinical signs of EAE reduced the severity of disease, however, their combination resulted in enhanced amelioration of disease. These results suggest that use of RXR specific ligands may be highly effective when combined with PPAR-gamma agonists in the treatment of autoimmune demyelinating diseases such as multiple sclerosis (MS).
过氧化物酶体增殖物激活受体γ（PPAR-γ）是核受体超家族的成员，它作为PPAR-RXR异二聚体与视黄酸X受体（RXR）结合并与DNA结合。在实验性自身免疫性脑脊髓炎（EAE）中，EAE病程中脊髓内PPAR-γ的基因表达得到证实。在EAE临床症状出现时单独给予15-脱氧-（12,14）-前列腺素J2（15d-PGJ2）或9-顺式视黄酸（RA）可减轻疾病严重程度，然而，它们联合使用可增强疾病的改善效果。这些结果表明，在治疗诸如多发性硬化症（MS）等自身免疫性脱髓鞘疾病时，RXR特异性配体与PPAR-γ激动剂联合使用可能非常有效。
