Loureirin B Promotes Axon Regeneration by Inhibiting Endoplasmic Reticulum Stress: Induced Mitochondrial Dysfunction and Regulating the Akt/GSK-3β Pathway after Spinal Cord Injury.

Abstract:

:Axon retraction greatly limits functional recovery after spinal cord injury (SCI) and neuron polarization, which affects processes including axon formation and development, is a promising target for promoting axon regeneration. Increasing microtubule stability has been demonstrated to improve intrinsic axon regeneration processes and is critically related to endoplasmic reticulum (ER)-mitochondria interactions. We used real-time polymerase chain reaction, Western blotting, and immunofluorescence to screen a variety of natural compounds, and found that Loureirin B (LrB) effectively promoted neuron polarization and axon regeneration in vitro and in vivo. LrB significantly inhibited ER stress and thereby promoted mitochondrial functions by regulating mitochondrial fusion. Further, LrB reactivated the Akt/GSK-3β pathway, which plays critical roles in cell survival and microtubule stabilization. Taken together, our results suggest that the effects of LrB on neuron regeneration involve the inhibition of ER stress-induced mitochondrial dysfunction and activation of the Akt/GSK-3β pathway, which further promotes microtubule stabilization. LrB may therefore be a promising candidate for facilitating recovery following SCI.

journal_name

J Neurotrauma

journal_title

Journal of neurotrauma

authors

Wang Q,Cai H,Hu Z,Wu Y,Guo X,Li J,Wang H,Liu Y,Liu Y,Xie L,Xu K,Xu H,He H,Zhang H,Xiao J

doi

10.1089/neu.2018.5966

subject

Has Abstract

pub_date

2019-06-15 00:00:00

pages

1949-1964

issue

12

eissn

0897-7151

issn

1557-9042

journal_volume

36

pub_type

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