Inhibition of mTOR Pathway by Rapamycin Decreases P-glycoprotein Expression and Spontaneous Seizures in Pharmacoresistant Epilepsy

2017 ◽  
Vol 61 (4) ◽  
pp. 553-562 ◽  
Author(s):  
Xiaosa Chi ◽  
Cheng Huang ◽  
Rui Li ◽  
Wei Wang ◽  
Mengqian Wu ◽  
...  
2017 ◽  
Vol 24 (2) ◽  
pp. 186-200 ◽  
Author(s):  
Rebecca M. Hauser ◽  
David C. Henshall ◽  
Farah D. Lubin

Epilepsy is a common and devastating neurological disorder characterized by recurrent and unprovoked spontaneous seizures. One leading hypothesis for the development and progression of epilepsy is that large-scale changes in gene transcription and protein expression contribute to aberrant network restructuring and hyperexcitability, resulting in the genesis of repeated seizures. Current research shows that epigenetic mechanisms, including posttranslational alterations to the proteins around which DNA is coiled, chemical modifications to DNA, and the activity of various noncoding RNA molecules exert important influences on these gene networks in experimental epilepsy. Key findings from animal models have been replicated in humans using brain tissue obtained from living patients at the time of neurosurgical resection for pharmacoresistant epilepsy. These findings have spurred efforts to target epigenetic processes to disrupt or modify epilepsy in experimental models with varying degrees of success. In this review, we will (1) summarize the epigenetic mechanisms implicated in epileptogenesis and epilepsy, (2) explore the influence of metabolic factors on epigenetic mechanisms, and (3) assess the potential of using epigenetic markers to support diagnosis and prognosis. Translation of these findings may guide the development of molecular biomarkers and novel therapeutics for prevention or modification of epileptic disorders.


2018 ◽  
Vol 16 (4) ◽  
pp. 5-9 ◽  
Author(s):  
Ivan V. Chernykh ◽  
Alexey V. Shchulkin ◽  
Natalya M. Popova ◽  
Ekaterina E. Kirichenko ◽  
Elena N. Yakusheva

P-glycoprotein (Pgp, ABCB1-protein) is a membrane efflux protein transporter located in hepatocytes, enterocytes, epithelial cells of the proximal renal tubules, histogematic barriers, and also in tumor cells, which releases the substrates from cells and plays an important role in pharmacokinetics of drugs. Inhibition of Pgp functional activity is promising for increasing the effectiveness of drug treatment of oncological diseases and pharmacoresistant epilepsy, but today no synthetic inhibitor of the transporter can be used in clinical practice because of side effects development. The aim of this review is to prove the relevance to use polysaccharides of plant origin, their derivatives and chemical modifications as effective, safe and cost-effective inhibitors of the transporter protein. The article describes the chemical structure of Pgp substrates and inhibitors, the ability to predict the drugs belonging to the transporter protein substrates or inhibitors. Some results of investigations of the belonging of oligo- and polysaccharides to Pgp substrates and inhibitors are presented. They are premises for carrying out appropriate experiments for polysaccharides of plant origin both in vitro and in vivo.


2015 ◽  
Vol 117 (5) ◽  
pp. 1233-1239 ◽  
Author(s):  
Li Wang ◽  
Changyuan Wang ◽  
Yongming Jia ◽  
Zhihao Liu ◽  
Xiaohong Shu ◽  
...  

2008 ◽  
Vol 41 (05) ◽  
Author(s):  
E Jaquenoud-Sirot ◽  
B Knezevic ◽  
G Perla Morena ◽  
P Baumann ◽  
CB Eap

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
M Reis ◽  
RJ Ferreira ◽  
MMM Santos ◽  
DJVA dos Santos ◽  
J Molnár ◽  
...  

Author(s):  
Chudy Darko ◽  
Almahariq Fadi ◽  
Francišković Ivica ◽  
Marčinković Petar

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