Honors College Thesis

 

The Effect of Riluzole on P2X7 and EAAT2 Expression by Inducible Neural Progenitor Cell (iNPC)-derived Astrocytes Public Deposited

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https://ir.library.oregonstate.edu/concern/honors_college_theses/p55480374

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  • Although it is the first drug approved for usage to treat amyotrophic lateral sclerosis (ALS), riluzole’s mechanism of action is unknown and its therapeutic quality is hampered by its relatively short window of effectiveness. P2X7 is a purine receptor found in astrocytes and other cells, which increases calcium concentrations within them; elevated expression of P2X7 has previously been connected to higher rates of motor neuron death resulting from peroxynitrite formation and the activation of an associated apoptotic pathway. Reduced levels of the glutamate transporter EAAT2 are also associated with motor neuron death due to the activation of an apoptotic pathway, distinct from the one previously described, caused by elevated glutamate levels in the environment of motor neurons. Riluzole’s effects may derive in part from its influence over P2X7 and EAAT2 expression levels. Understanding riluzole’s mechanism of action is important because it may reveal potential factors contributing to its weaknesses as a treatment for ALS. This knowledge can be used to open lines of inquiry which can lead to the discovery of ways to adjust existing treatment regimens such that more positive patient health outcomes can be obtained. Furthermore, it may foster the discovery of better treatments for ALS.
  • Keywords: ALS, P2X7, EAAT2, riluzole, astrocytes, SOD1
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