Investigating the neuroprotective effects of pharmacological Bax inhibition

Abstract

Apoptosis is a highly regulated mode of cell death in the development and progression of neurodegenerative diseases and neuronal injuries. The Bcl-2 protein family are key regulators of the intrinsic mitochondrial apoptotic pathway. Our lab and others have demonstrated that the pro-apoptotic Bcl-2 family member Bax plays a prominent role in regulating neuronal apoptosis. Eltrombopag has been identified as an inhibitor of Bax in in vitro non-neuronal cells. We hypothesized that Eltrombopag would provide neuroprotection against Bax-mediated apoptosis in neurons. Specifically, we investigated whether Eltrombopag could inhibit apoptosis induced by ER-stress using Thapsigargin and oxidative stress using 6OHDA, both of which we have previously shown to be Bax-mediated. In both models of neuronal apoptosis, Eltrombopag administration prevented cytochrome-3 release, inhibited caspase-3 activation, and attenuated neuronal death. Our findings suggest that utilizing Eltrombopag as an inhibitor of the Bcl-2 family protein Bax may be therapeutic in attenuating disease and injury-associated neuronal apoptosis

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Last time updated on 20/02/2024

This paper was published in Scholarship@Western.

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