SHM Converge Scientific Abstract ePoster Gallery-Reduced Autophagy by Chlorpromazine and Phenothiazines in Cerebral Ischemia/Reperfusion Injury

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This study examined how chlorpromazine and promethazine (CP) protect the brain after ischemia/reperfusion (I/R) injury, with a focus on the endoplasmic reticulum stress pathway PERK-eIF2α and its link to autophagy and apoptosis.<br /><br />In a rat middle cerebral artery occlusion model, I/R injury increased markers of endoplasmic reticulum stress and autophagy, including Bip, p-PERK, p-eIF2α, ATG12, and LC3II/I. CP treatment significantly reduced these markers at both the mRNA and protein levels. CP also shifted apoptosis-related proteins toward cell survival by increasing anti-apoptotic Bcl-XL and decreasing pro-apoptotic BAX.<br /><br />Similar effects were seen in SH-SY5Y cells subjected to oxygen-glucose deprivation/reoxygenation. CP improved cell viability, reduced cell death, and lowered autophagy and apoptosis. A PERK inhibitor (GSK2656157) produced comparable protective effects, and combining the inhibitor with CP did not add much further benefit, suggesting CP acts largely through the PERK-eIF2α pathway.<br /><br />The study also tested whether CP’s benefits depended on body temperature control. Lowering temperature minimally or not at all did not meaningfully change CP’s neuroprotective effects, indicating that CP’s protection is not mainly due to hypothermia.<br /><br />Overall, the findings suggest that CP reduces cerebral I/R injury by suppressing ER stress-induced autophagy and apoptosis through inhibition of the PERK-eIF2α pathway. This pathway may be an important therapeutic target for stroke treatment.

Asset Subtitle

Ho Jun Yun

Meta Tag

Author List Ho Jun Yun, Xiaokun Geng, Yuchuan Ding, Yuchuan Ding

Category Research

Concept Cerebral Ischemia/Reperfusion Injury

Concept PERK-eIF2α Pathway

Concept Endoplasmic Reticulum Stress

Concept Chlorpromazine

Concept Promethazine

Concept PERK-eIF2a Pathway

Distinguished Non-Finalist

Presenter Organization Wayne State University School of Medicine

Presenting Author Ho Jun Yun

Track Other

Keywords

chlorpromazine

promethazine

cerebral ischemia-reperfusion

PERK-eIF2α pathway

endoplasmic reticulum stress

autophagy

apoptosis

neuroprotection

stroke treatment

Bip

Cerebral Ischemia/Reperfusion Injury

PERK-eIF2α Pathway

Endoplasmic Reticulum Stress

Chlorpromazine

Promethazine