Iron dysregulation contributes to neurodegenerative diseases

Jamsey

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“Past neuroscience research consistently found a link between deviations from the "normal" iron metabolism, also known as iron dysregulation, and different neurodegenerative diseases, including Parkinson's disease (PD) and Multiple Sclerosis (MS). Specifically, brain regions associated with these diseases have been found to be often populated by microglia (i.e., resident immune cells) packed with Iron.”

“"For years it has been known that iron accumulates in affected brain regions in PD, MS and other neurodegenerative diseases," Timothy Hammond, one of the researchers who carried out the study, told MedicalXpress. "This is something we can see in patients using MRI imaging, where it has been shown that iron levels increase over the course of the disease. We also had our own data from progressive MS patients showing iron dysregulation in brain microglia, the resident immune cells of the brain."”
“Ferroptosis is a form of cell death that is mediated by iron-dependent lipid peroxidation, a process that damages lipids by oxidizing them. In their paper, the researchers' hypothesized that iron-laden microglia are susceptible to ferroptosis and that this might play a role in neurodegenerative diseases.”

Using a series of genetic and experimental techniques, they then showed that these microglia are highly responsive to iron and also susceptible to ferroptosis.

In addition, the team showed that an overload of iron causes a shift in the microglial transcriptional state, which overlaps with a transcriptomic signature observed in microglia in brain tissuefrom deceased patients with PD. When they removed microglia from their tri-culture system, Hammond and his colleagues observed that iron-induced neurotoxicity in the system significantly slowed down. This suggests that microglia responses to iron overload play a crucial role in neurodegeneration.”

“This study is one of the first to show how iron-laden microglia might contribute to different PD and other neurodegenerative diseases. In the future, it could pave the way for new important discoveries, potentially informing the development of new therapeutic interventions for these diseases.

"We believe microglia are actually trying protect neurons by taking up toxic iron and storing it safely, but over time the microglia become overwhelmed and die, releasing the stored iron and causing the neurons to die too,"”
 

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