Anavex Life Sciences Corp (AVXL)

[georgejjl]

Protein misfolding and aggregation is implicated in the pathogenesis of PD, and the regulation of GRP78/BiP is critical for proper functioning of the UPR. As highlighted in this review, several studies have attempted to unravel the mechanism behind ER stress by targeting GRP78/BiP and the UPR as a way of halting dopaminergic neuronal loss in PD. Although it is established that GRP78/BiP is an essential chaperone in the UPR, studies discussed in this review indicate that the expression of GRP78/BiP is altered in various models of PD depending on the cell type and toxin used in inducing neuronal damage. Consequently, various neuroprotective agents induce the upregulation or downregulation of GRP78/BiP in response to the ER stress-inducing agent in these PD models to promote the survival of dopaminergic neurons. Also, evidence from this review indicate that a translational potential exists for the regulation of GRP78/BiP activity; however, further investigations are needed to properly understand the involvement of GRP78/BiP in the protection of neurons against degeneration in PD. This knowledge would be valuable in designing novel remedies targeted at combating PD and other neurodegenerative disorders linked to the aggregation of misfolded proteins.

https://www.hindawi.com/journals/aps/2019/2706783/

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