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Pharmacological research

Pharmacological research

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Pleiotropic role of mGluR7/MAPK signaling in the protection of intelectin-1 against cerebral ischemia-reperfusion injury

Published:16 April 2025 DOI: 10.1016/j.phrs.2025.107735
Xiaochen Niu , Bodong Wang , Aizhen Zhao , Wenwen Yang , Ning Li , Wenzhen Shi , Wangrui Lei , Ying Cheng , Baoying Wang , Yang Yang , Songdi Wu , Ye Tian

Abstract

Acute ischemic stroke (AIS) is a serious neurological condition with limited treatment options available. Studies have shown that levels of the protein intelectin-1 (ITLN-1) are linked to stroke severity and poor neurological outcomes. This study aimed to evaluate the role and molecular mechanisms of ITLN-1 in AIS. This study found that ITLN-1 is widely expressed in various brain regions, while ITLN-1 levels were significantly decreased in the blood and brain tissues of ischemic stroke patients. ITLN-1 overexpression reduced neuronal damage and motor deficits in transient middle cerebral artery occlusion/reperfusion (tMCAO/R) treated mice. Treatment with Rh-omentin or ITLN-1 overexpression also had a protective effect in cellular injury models. RNA-seq analysis revealed that ITLN-1 impacts specific genes and pathways, particularly those related to mGluR7. Molecular docking and CO-IP analysis confirmed that ITLN-1 directly binds to and interacts with mGluR7. The study also showed that the ITLN-1/mGluR7 axis regulates MAPK cascades (ERK and p38) to reduce cerebral oxidative stress, mitochondrial dysfunction, and cell death. Additionally, the compound AKR-501 was found to have a protective effect against cerebral ischemia by modulating the ITLN-1/mGluR7/MAPK cascades. Overall, these findings suggest that targeting ITLN-1 could be a promising therapeutic approach for managing AIS, with important clinical implications.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
Ascorbic Acid 50-81-7 C6H8O6 2018 suppliers $6.00-$2380.00
Ascorbic Acid 50-81-7 C6H8O6 2018 suppliers $6.00-$2380.00
Ascorbic Acid 50-81-7 C6H8O6 2018 suppliers $6.00-$2380.00
Ascorbic Acid 50-81-7 C6H8O6 2018 suppliers $6.00-$2380.00
Dimethyl sulfoxide 67-68-5 C2H6OS 1932 suppliers $5.00-$120900.00
Dimethyl sulfoxide 67-68-5 C2H6OS 1932 suppliers $5.00-$120900.00
Dimethyl sulfoxide 67-68-5 C2H6OS 1932 suppliers $5.00-$120900.00
Dimethyl sulfoxide 67-68-5 C2H6OS 1932 suppliers $5.00-$120900.00
D(+)-Glucose 50-99-7 C6H12O6 1505 suppliers $6.00-$26950.00
D(+)-Glucose 50-99-7 C6H12O6 1505 suppliers $6.00-$26950.00

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