Modulation of Sel1L can alleviate altered ER homeostasis towards white matter damage in CKD-stroke complex

Modulation of Sel1L can alleviate altered ER homeostasis towards white matter damage in CKD-stroke complex

Abstract Stroke is one of the major causes of mortality and long-term disability worldwide. Chronic-kidney-disease (CKD) is a condition where patients have shown increased vulnerability to stroke with poor functional and cognitive outcomes. Impaired cerebral autoregulation in CKD patients may impose...

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Main Authors: Aishika Datta, Priti Patale, Debarati Ghosh, Priya Jagtap, Jinagna Shah, Mounika Katamneni, Anita Kumari, Nikita Malik, Gautam Karmarkar, Anirban Barik, Bijoyani Ghosh, Pooja Dhakne, Vinod Pathulothu, Deepaneeta Sarmah, Harpreet Kaur, Nikita Rana, Rajeshwari Rathod, Anupom Borah, Pinaki Sengupta, Pallab Bhattacharya
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08100-0
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Summary:Abstract Stroke is one of the major causes of mortality and long-term disability worldwide. Chronic-kidney-disease (CKD) is a condition where patients have shown increased vulnerability to stroke with poor functional and cognitive outcomes. Impaired cerebral autoregulation in CKD patients may impose a high risk of stroke. To date, the mechanism of worsened stroke outcomes in CKD patients are limitedly understood. Alterations of endoplasmic-reticulum (ER) homoeostasis via modification of Sel1L-Hrd1 complex is one of the many cellular events that gets triggered following both CKD and stroke leading to accumulation of misfolded proteins, culminating in ER-stress. Therefore, the present study aims to explore the involvement of Sel1L mediated altered ER functions towards worsening of stroke outcome in CKD and further its crucial role towards white matter damage. CKD-stroke complex was induced in male Sprague-Dawley rats followed by middle-cerebral-artery occlusion. At 24 h and 7th day of reperfusion, animals were subjected to behavioral analysis followed by euthanasia, brain harvest and molecular studies. CKD-Stroke-complex animals showed aggravated neurofunctional and cognitive impairment which were further normalized by treatment of an ER-stress inhibitor. This indicates exacerbated stroke outcome in CKD-stroke-complex may be mediated by imbalanced ER-homeostasis due to decreased Sel1L expression leading to enhanced cellular death and neurodegeneration.
ISSN:2399-3642

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