Ferroptosis-centered Disease Response Information

General Information of the Disease (ID: DIS00067)
Name
Cognitive disorder
ICD
ICD-11: 6D71
Full List of Target(s) of This Ferroptosis-centered Disease
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Driver
Responsed Disease Diabetes-induced cognitive dysfunction [ICD-11: 6D71]
Responsed Drug Liraglutide Approved
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model mHNs (Mouse hippocampal neurons)
In Vivo Model
Male diabetic db/db mice and nondiabetic littermate db/m mice that were 4 weeks of age were purchased from Changzhou Cavens Experimental Animal Co., Ltd. After 1week of adaptive feeding, 20 db/db mice were randomly divided into two groups: a model group (db/db, n = 10) and a treatment group (LIRA, n = 10). Another 10 db/m mice were used as the control group (db/m, n = 10). After feeding to 10weeks old, the LIRA group was given liraglutide (CSN11311, CSNpharm, China) diluent (200 ug/kg/d) by intraperitoneal injection for 5 weeks, with equivoluminal 0.9% saline intraperitoneally administered to the other two groups.

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Response regulation Liraglutide was shown to prevent ferroptosis in the hippocampus by elevating the expression of GPX4 and SLC7A11 and suppressing the excessive amount of ACSL4. LIRA can reduce oxidative stress, lipid peroxidation and iron overload in diabetes-induced cognitive dysfunction and further inhibit ferroptosis, thereby weakening the damage to hippocampal neurons and synaptic plasticity and ultimately restoring cognitive function.
Cystine/glutamate transporter (SLC7A11)
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Diabetes-induced cognitive dysfunction [ICD-11: 6D71]
Responsed Drug Liraglutide Approved
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model mHNs (Mouse hippocampal neurons)
In Vivo Model
Male diabetic db/db mice and nondiabetic littermate db/m mice that were 4 weeks of age were purchased from Changzhou Cavens Experimental Animal Co., Ltd. After 1week of adaptive feeding, 20 db/db mice were randomly divided into two groups: a model group (db/db, n = 10) and a treatment group (LIRA, n = 10). Another 10 db/m mice were used as the control group (db/m, n = 10). After feeding to 10weeks old, the LIRA group was given liraglutide (CSN11311, CSNpharm, China) diluent (200 ug/kg/d) by intraperitoneal injection for 5 weeks, with equivoluminal 0.9% saline intraperitoneally administered to the other two groups.

    Click to Show/Hide
Response regulation Liraglutide was shown to prevent ferroptosis in the hippocampus by elevating the expression of GPX4 and SLC7A11 and suppressing the excessive amount of ACSL4. LIRA can reduce oxidative stress, lipid peroxidation and iron overload in diabetes-induced cognitive dysfunction and further inhibit ferroptosis, thereby weakening the damage to hippocampal neurons and synaptic plasticity and ultimately restoring cognitive function.
References
Ref 1 Liraglutide Alleviates Cognitive Deficit in db/db Mice: Involvement in Oxidative Stress, Iron Overload, and Ferroptosis. Neurochem Res. 2022 Feb;47(2):279-294. doi: 10.1007/s11064-021-03442-7. Epub 2021 Sep 4.