How iron can drive neurodegeneration

Article Neurosciences

Microglia ferroptosis is regulated by SEC24B and contributes to neurodegeneration

Sean K. Ryan et al.

Summary: Iron dysregulation is associated with multiple neurodegenerative diseases, including Parkinson's disease. In this study, it is found that iron-loaded microglia are responsive to iron and susceptible to ferroptosis, a form of cell death that is dependent on iron. Iron overload also induces a shift in the microglial transcriptional state that is similar to the transcriptomic signature found in postmortem brain microglia of Parkinson's disease. The removal of microglia delays iron-induced neurotoxicity, suggesting the contribution of microglial response to neurodegeneration.

NATURE NEUROSCIENCE (2023)

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Article Cell & Tissue Engineering

Iron accumulation induces oxidative stress, while depressing inflammatory polarization in human iPSC-derived microglia

Boyd Kenkhuis et al.

Summary: Iron accumulation in microglia is associated with neuroinflammation in neurodegenerative disorders, but iron treatment does not induce pro-inflammatory activation and instead dampens it while inducing oxidative stress.

STEM CELL REPORTS (2022)

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Article Medicine, General & Internal

Trial of Deferiprone in Parkinson's Disease

David Devos et al.

Summary: In a 36-week trial involving participants with early Parkinson's disease who had not received levodopa, treatment with the iron chelator deferiprone led to worse scores in measures of parkinsonism compared to placebo.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

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Article Clinical Neurology

Regional brain iron associated with deterioration in Alzheimer's disease: A large cohort study and theoretical significance

Scott Ayton et al.

Summary: This paper proposes an updated version of the iron hypothesis in Alzheimer's disease, suggesting that brain iron levels are associated with disease progression and may play a role in neurodegeneration. Further research is needed to validate the hypothesis.

ALZHEIMERS & DEMENTIA (2021)

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Article Neurosciences

Iron loading is a prominent feature of activated microglia in Alzheimer's disease patients

Boyd Kenkhuis et al.

Summary: Brain iron accumulation accelerates disease progression in Alzheimer patients with amyloid-beta. Activated microglia with increased iron accumulation influence the functional phenotype of cells, especially in conjunction with amyloid-beta. Spatial analysis showed that iron-accumulating microglia predominantly infiltrated A beta-plaques in the brain.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2021)

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Article Clinical Neurology