IDOL Exacerbates Cerebral ischemia/reperfusion injury by down-regulating LDLR expression in mice

Published: 30 December 2025| Version 2 | DOI: 10.17632/bs3v3whf8b.2
Contributors:
, Xiaoyu Duan,
,
,
,
,

Description

Low-density lipoprotein receptor (LDLR) is crucial in regulating cholesterol metabolism. LDLR decreases cholesterol levels through receptor-mediated endocytosis. Inducible degrader of LDLR (IDOL) inhibits the uptake of low-density lipoprotein (LDL) by down-regulating the expression of LDLR, which leads to hypercholesterolemia. Research has demonstrated that the development of cerebral ischemia/reperfusion injury (CI/RI) is associated with elevated cholesterol levels in the brain. Our results showed that compared to normal mice, IDOL was highly expressed, and the expression of LDLR was significantly decreased in the MCAO mice. Knockout of IDOL can downregulate the expression of LDLR, upregulate the expression of Apolipoprotein E (ApoE) and Caspase-3, promote the occurrence of neuroinflammation and cell apoptosis in the MCAO mice, and play a particular protective role in CI/RI mice.

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