Metformin Activates AMPK to Restrain Mitochondrial ROS-Driven Necroptosis in Cadmium Neurotoxicity - PubMed
a day ago
- #metformin
- #necroptosis
- #neurodegeneration
- Cadmium (Cd) exposure is a risk factor for neurodegeneration, contributing to neuronal loss via necroptosis.
- AMPK-mtROS-RIPK1/RIPK3-MLKL axis identified as a central driver of Cd neurotoxicity and a target for metformin.
- Metformin preserves hippocampal neuronal integrity, reduces mtROS, and prevents necrosome assembly in Cd-exposed models.
- Inhibition or deletion of RIPK1, RIPK3, or MLKL attenuates Cd-induced necrosis, mimicking metformin's effects.
- Metformin restores Cd-suppressed AMPK activity, which is crucial for suppressing mtROS and necroptotic signaling.
- Scavenging mtROS reduces necroptosis and synergizes with metformin to disrupt RIPK3-MLKL complex formation.
- Findings support repurposing metformin for neurodegenerative conditions involving necroptosis.