Apoferritin Attenuates Experimental Allergic Encephalomyelitis in SJL Mice

Levine, Steven M.; Maiti, Smarajit; Emerson, Mitchell R.; Pedchenko, Tetyana V.

doi:10.1159/000065694

Cited by 19 publications

(15 citation statements)

References 51 publications

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“…Thus, to test this possibility, apoferritin was administered to SJL mice with EAE. Apoferritin was found to suppress disease activity in EAE mice, while injections of iron, which increased serum ferritin levels, failed to ameliorate the disease course 117. It was suggested that the ferritin synthesized in response to iron injections quickly acquired the injected iron and lost some or most of its therapeutic potential since ferritin loaded with iron can release iron, especially when exposed to superoxide anion radical or nitric oxide 118,119.…”

Section: Therapeutic Approaches Targeting Pathogenic Mechanism Involvmentioning

confidence: 99%

The Role of Iron in the Pathogenesis of Experimental Allergic Encephalomyelitis and Multiple Sclerosis

Levine

Chakrabarty

2004

Annals of the New York Academy of Sciences

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138

105

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Multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE), are autoimmune disorders resulting in demyelination in the central nervous system (CNS). Pathologically, the blood-brain barrier becomes damaged, macrophages and T cells enter into the CNS, oligodendrocytes and myelin are destroyed, astrocytes and microglia undergo gliosis, and axons become transected. Data from several biochemical and pharmacological studies indicate that free radicals participate in the pathogenesis of EAE, and iron has been implicated as the catalyst leading to their formation. The primary focus of this article is the examination of the role of iron in the pathogenesis of MS and EAE. Particular attention will be paid to the role and distribution of iron and proteins involved with iron metabolism (e.g., transferrin, ferritin, heme oxygenase-1, etc.) in normal and disease states of myelin. Furthermore, therapeutic interventions aimed at iron, iron-binding proteins, and substrates or products of iron-catalyzed reactions leading to free radical production will be discussed.

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Section: Therapeutic Approaches Targeting Pathogenic Mechanism Involvmentioning

confidence: 99%

The Role of Iron in the Pathogenesis of Experimental Allergic Encephalomyelitis and Multiple Sclerosis

Levine

Chakrabarty

2004

Annals of the New York Academy of Sciences

Self Cite

138

105

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“…Apoferritin can bind large amounts of iron and protect against oxidative injury (discussed in LeVine et al, 2002). When it was administered during active disease (750 μg, twice daily), apoferritin lessened clinical signs of EAE in SJL female mice given PLP peptide as an encephalitogen and pertussis toxin injections (LeVine et al, 2002) (Table 1).…”

Section: Iron Chelation In Eaementioning

confidence: 99%

“…When it was administered during active disease (750 μg, twice daily), apoferritin lessened clinical signs of EAE in SJL female mice given PLP peptide as an encephalitogen and pertussis toxin injections (LeVine et al, 2002) (Table 1). …”

Section: Iron Chelation In Eaementioning

confidence: 99%

Iron Chelation and Multiple Sclerosis

2013

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Histochemical and MRI studies have demonstrated that MS (multiple sclerosis) patients have abnormal deposition of iron in both gray and white matter structures. Data is emerging indicating that this iron could partake in pathogenesis by various mechanisms, e.g., promoting the production of reactive oxygen species and enhancing the production of proinflammatory cytokines. Iron chelation therapy could be a viable strategy to block iron-related pathological events or it can confer cellular protection by stabilizing hypoxia inducible factor 1α, a transcription factor that normally responds to hypoxic conditions. Iron chelation has been shown to protect against disease progression and/or limit iron accumulation in some neurological disorders or their experimental models. Data from studies that administered a chelator to animals with experimental autoimmune encephalomyelitis, a model of MS, support the rationale for examining this treatment approach in MS. Preliminary clinical studies have been performed in MS patients using deferoxamine. Although some side effects were observed, the large majority of patients were able to tolerate the arduous administration regimen, i.e., 6–8 h of subcutaneous infusion, and all side effects resolved upon discontinuation of treatment. Importantly, these preliminary studies did not identify a disqualifying event for this experimental approach. More recently developed chelators, deferasirox and deferiprone, are more desirable for possible use in MS given their oral administration, and importantly, deferiprone can cross the blood–brain barrier. However, experiences from other conditions indicate that the potential for adverse events during chelation therapy necessitates close patient monitoring and a carefully considered administration regimen.

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“…48 Reactive Oxygen Species participate in the pathogenesis of allergic encephalomyelitis, whereas the infusion of apoferritin in experimental animals may induce a remission status. 49 Thyroid hormone upregulates ferritin genes' expression, and elevated serum ferritin levels have been reported in patients with subacute thyroiditis, which were correlated with disease activity. These levels were higher, as compared to patients with Graves' disease and Hashimoto's thyroiditis.…”

Section: The Role Of Iron In Inflammatory and Neoplastic Diseasesmentioning

confidence: 99%