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Iron chelation as a therapeutic approach for neurodegenerative disease symptoms

Iron chelation as a therapeutic approach for neurodegenerative disease symptoms: Given the evidence of iron accumulation in Alzheimer′s disease, iron removal from certain brain regions without causing a systematic iron deficiency should be considered. Based on this drugs such as clioquinol, PBT2, and deferiprone have been developed or this neurodegenerative conditions. Earlier studies have explored the therapeutic efficacy of iron removal with intramuscular injections of the iron chelator desferrioxamine which leads to a significant reduction in cognitive decline. Intranasal deferoxamine reversed iron-induced memory deficits, inhibits amyloid beta peptide aggregation in mouse models of Alzheimer′s disease. deferoxamine improved the motoric deficits and pathology in the α-synuclein Parkinson′s disease mouse model.

Also, 5-Chloro-7-iodo-quinolin-8-ol (clioquinol; chelator of iron, copper, and zinc) reduced amyloid protein deposition in the brain and prevent memory impairment in Alzheimer′s disease animal model.  Clioquinol was shown to rescue Parkinsonism and dementia phenotypes of the tau knockout mouse. Likewise, PBT2, (chelator derivative of clioquinol) promoted amyloid plaque degradation. This PBT2 also redirected excess released metals to neuronal compartments where the metals are needed.

Iron chelation for treating neurodegenerative disease symptoms
Iron chelation for treating neurodegenerative disease symptoms: Given the evidence of iron accumulation in Alzheimer′s disease, iron removal from certain brain regions should be considered. Adapted from Rouault et al., 2013.

Iron removal in Parkinson′s disease was shown to reduce iron levels and prevent toxicity in a mouse model of Parkinson′s disease. Long-term treatment of the patient with deferiprone showed a rapid decrease in iron.

Challenges of using iron chelation for neurodegenerative disease.

One of the challenges of using iron chelation is the inability of large molecules eg. desferrioxamine to penetrate the blood-brain barrier, which is important in order to remove excess iron from the brain. Secondly, there is a risk of depletion of the peripheral iron from plasma. However, with all these challenges, iron chelation still stands out as a prospective therapeutic approach for neurodegenerative diseases.

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