Peroxisome proliferator activated receptor gamma (PPAR纬) as a therapeutic target for improvement of cognitive performance in Fragile-X

详细信息    查看全文

• 作者：Mohammad Jodeiri Farshbaf ; Kamran Ghaedi ; Mahsa Shirani ; Mohammad Hossein Nasr-Esfahani
• 关键词：AMPAR ; 伪-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor ; CNS ; central nervous system ; ECM ; extra cellular matrix ; FMR1 gene ; Fragile X mental retardation 1 gene ; FMRP ; Fragile-X mental retardation protein ; FXS ; Fragile X syndrome ; GLUT-3 ; glucose transporter 3 ; Gp1 ; group 1 ; IDE ; insulin-degrading enzyme ; LTD ; long-term depression ; LTP ; long-term potentiation ; mGluR ; metabotropic glutamate receptor ; MMPs ; matrix metalloproteinases ; mTOR ; mammalian target of rapamycin ; NMDA ; N-methy
• 刊名：Medical Hypotheses
• 出版年：March, 2014
• 年：2014
• 卷：82
• 期：3
• 页码：291-294
• 全文大小：259 K

文摘

Rare disorders leading to intellectual disability, such as Fragile X syndrome (FXS) alter synaptic plasticity. Ligand identification of orphan nuclear receptors has led to the discovery of many signaling pathways and has revealed a direct link of nuclear receptors with human conditions such as mental retardation and neurodegenerative diseases. PPAR纬 agonists can act as neuroprotective agents, promoting synaptic plasticity and neurite outgrowth. Therefore, selective PPAR纬 agonists are good candidates for therapeutic evaluation in intellectual disabilities. Preliminary results suggest that PPAR纬 agonists such as Pioglitazone, Rosiglitazone and synthetic agonist, GW1929, are used as the therapeutic agent in neurological disorders. These components interact with intracellular transduction signals (e.g. GSK3尾, PI3K/Akt, Wnt/尾-Catenin, Rac1 and MMP-9). It seems that interaction with these pathways can improve memory recognition in FXS animal models. The present hypothesis consists of enhancing synaptic plasticity that may then rescue the learning and memory in FXS. This will open many new therapeutic avenues for a variety of human diseases.