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The role of iron in brain ageing and neurodegenerative disorders

TLDR
MRI can often identify changes in iron homoeostasis, thus providing a potential diagnostic biomarker of neurodegenerative diseases and an important avenue to reduce iron accumulation is the use of iron chelators that are able to cross the blood-brain barrier, penetrate cells, and reduce excessive iron accumulation, thereby affording neuroprotection.
Abstract
Summary In the CNS, iron in several proteins is involved in many important processes such as oxygen transportation, oxidative phosphorylation, myelin production, and the synthesis and metabolism of neurotransmitters. Abnormal iron homoeostasis can induce cellular damage through hydroxyl radical production, which can cause the oxidation and modification of lipids, proteins, carbohydrates, and DNA. During ageing, different iron complexes accumulate in brain regions associated with motor and cognitive impairment. In various neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, changes in iron homoeostasis result in altered cellular iron distribution and accumulation. MRI can often identify these changes, thus providing a potential diagnostic biomarker of neurodegenerative diseases. An important avenue to reduce iron accumulation is the use of iron chelators that are able to cross the blood–brain barrier, penetrate cells, and reduce excessive iron accumulation, thereby affording neuroprotection.

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Iron neurochemistry in Alzheimer's disease and Parkinson's disease: targets for therapeutics

TL;DR: The current knowledge on iron homeostasis in the brain is discussed and how alterations in brain iron metabolism affect neuronal function with emphasis on iron dysregulation in Alzheimer′s and Parkinson′s diseases is explored.
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History and progress of hypotheses and clinical trials for Alzheimer’s disease

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References
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Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death

TL;DR: This paper identified the small molecule ferrostatin-1 as a potent inhibitor of ferroptosis in cancer cells and glutamate-induced cell death in organotypic rat brain slices, suggesting similarities between these two processes.
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Astrocyte–endothelial interactions at the blood–brain barrier

TL;DR: Specific interactions between the brain endothelium, astrocytes and neurons that may regulate blood–brain barrier function are explored to lead to the development of new protective and restorative therapies.
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Microglia-mediated neurotoxicity: uncovering the molecular mechanisms

TL;DR: Overactivated microglia can be detected using imaging techniques and therefore this knowledge offers an opportunity not only for early diagnosis but, importantly, for the development of targeted anti-inflammatory therapies that might slow or halt the progression of neurodegenerative disease.
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Reactive microglia are positive for HLA‐DR in the substantia nigra of Parkinson's and Alzheimer's disease brains

TL;DR: The detected large numbers of HLA-DR-positive reactive microglia (macrophages) in the substantia nigra of all cases studied with Parkinson's disease and parkinsonism and suggest a frequent coexistence of DAT- and Parkinson-type pathology in elderly patients.
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