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Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
Published on: April 24, 2021
A molecular chaperone inducer protects neurons from ER stress
1Psychiatry, Department of Integrated Medicine, Division of Internal Medicine, Osaka University Graduate School of Medicine, Suita, Japan. kudo@psy.med.osaka-u.ac.jp
Cell Death and Differentiation
|December 1, 2007
Summary
BiP inducer X (BIX) activates the endoplasmic reticulum (ER) stress response, reducing neuronal cell death. This compound shows potential as a therapeutic agent for ER stress-related cerebral diseases.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Endoplasmic reticulum (ER) stress response mitigates unfolded protein accumulation.
- ER stress is implicated in neurodegenerative diseases and cerebral ischemia.
- BiP (immunoglobulin heavy-chain binding protein)/GRP78 (78 kDa glucose-regulated protein) is a key ER chaperone.
Purpose of the Study:
- To identify compounds that induce BiP/GRP78 expression.
- To investigate the therapeutic potential of BiP inducers for ER stress-related neuronal damage.
Main Methods:
- Screening for compounds that induce BiP/GRP78.
- Investigating the molecular pathway of BiP induction (ATF6 pathway).
- Evaluating the neuroprotective effects of BIX in cell culture and in a mouse model of cerebral ischemia.
Main Results:
- BiP inducer X (BIX) was identified, preferentially inducing BiP/GRP78.
- BIX-induced BiP expression is mediated by the ATF6 pathway.
- BIX pretreatment reduced neuroblastoma cell death from ER stress and decreased infarction area in mice with cerebral ischemia.
- BIX suppressed ER stress-induced apoptosis in the penumbra of ischemic brain tissue.
Conclusions:
- BIX induces BiP/GRP78 expression via the ATF6 pathway.
- BIX demonstrates neuroprotective effects against ER stress and cerebral ischemia.
- BIX is a potential therapeutic candidate for cerebral diseases linked to ER stress.
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