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Biomedicine & Pharmacotherapy

Biomedicine & Pharmacotherapy

IF: 6.9
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The roles and mechanisms of CDGSH iron-sulfur domain 1 in kainic acid-induced mitochondrial iron overload, dysfunction and neuronal damage

Published:24 April 2025 DOI: 10.1016/j.biopha.2025.118067
Jing Wang, Shuo Li, Haidong Xu, Jie Xue, Xiaorui Wan, Weilong Wu, Jiani Huang, Huiling Zhang, Zhenghong Qin, Yan Wang

Abstract

Maintaining mitochondrial function plays a crucial role in preventing and treating neurodegenerative diseases. CDGSH iron-sulfur domain 1 (CISD1), a NEET family protein localized on the mitochondrial outer membrane, regulates mitochondrial iron transport. However, the precise mechanism by which CISD1 modulates mitochondrial Fe2?+ remains unclear. In this study, we examine the link between aberrant iron metabolism and mitochondrial dysfunction using in vivo and in vitro excitotoxicity models. Our study also clarifies how CISD1 modulates KA-mediated excitotoxic neuronal damage. Overexpression of CISD1 reverses KA-induced mitochondrial iron overload and dysfunction. KA significantly downregulate the mitochondrial protein deacetylase SIRT1. SRT1460 (SIRT1-specific agonist) mitigates mitochondrial iron overload and restore CISD1 expression levels. Altogether, CISD1 protects against excitotoxic injury by mitigating mitochondrial iron overload, thereby providing a potential therapeutic target for neurodegenerative diseases.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
3,4,5-trimethoxy-N-(2-(3-(piperazin-1-ylmethyl)imidazo[2,1-b]thiazol-6-yl)phenyl)benzamide 925432-73-1 C26H29N5O4S 42 suppliers $51.00-$2520.00
3,4,5-trimethoxy-N-(2-(3-(piperazin-1-ylmethyl)imidazo[2,1-b]thiazol-6-yl)phenyl)benzamide 925432-73-1 C26H29N5O4S 42 suppliers $51.00-$2520.00
3,4,5-trimethoxy-N-(2-(3-(piperazin-1-ylmethyl)imidazo[2,1-b]thiazol-6-yl)phenyl)benzamide 925432-73-1 C26H29N5O4S 42 suppliers $51.00-$2520.00
3,4,5-trimethoxy-N-(2-(3-(piperazin-1-ylmethyl)imidazo[2,1-b]thiazol-6-yl)phenyl)benzamide 925432-73-1 C26H29N5O4S 42 suppliers $51.00-$2520.00

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