Possible relationship between Al/ferritin complex and Alzheimer's disease

Sole, P. De; Rossi, Cristina; Chiarpotto, M.; Ciasca, Gabriele; Bocca, Beatrice; Alimonti, Andrea; Bizzarro, Alessandra; Rossi, C; Masullo, Carlo

doi:10.1016/j.clinbiochem.2012.10.023

Cited by 52 publications

(39 citation statements)

References 28 publications

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“…Such an elevated Al amount is similar to that recently found in-vivo in the serum ferritin extracted from AD patients. 9 In contrast to the results shown in Fig. 2(b), an even higher amount of Al atoms (about 2000 Table II.…”

contrasting

confidence: 51%

“…Such a high value of Al and Al/Fe molar ratio is comparable to those found in recent studies on clinical patients. 4,9 These results suggest that this high amount of aluminum present in the apoferritin is likely conveyed by small ligands, such as citrate, which increases its solubility in physiological condition.…”

mentioning

confidence: 89%

“…3,4,9 Furthermore in this latter case also a very high Al/Fe molar ratio has been observed (in some specific case up to 6). 4,9 In this work, we investigate in-vitro by Sector Field Inductive Coupled Mass Spectroscopy (SF-ICP-MS) and Small-Angle X ray Scattering (SAXS) 11 the binding of Al to apoferritin with the aim to provide a better understanding of the mechanism underlying these two different uptakes of aluminum. In biological systems, aluminum can be found in its ionic form or complexed with small ligands which increase its solubility.…”

mentioning

confidence: 93%

“…This mechanism could have an important role in the pathological alterations typical of this and other neurodegenerative diseases as suggested in Ref. 9.…”

mentioning

confidence: 99%

“…1 Although ferritin has its main role in iron storage, several evidences suggest that it functions as a general metal detoxicant, binding in-vivo metals other than iron, such as aluminium (Al), 2-7 which has been recognized as a contributing factor in several neurological disorders. 8 The frequent isolation of Al-ferritin complexes, especially from Alzheimer Disease (AD) patients, 3,5,9,10 contributes to strengthen the suggested role for ferritin in metal toxicity. The observed increase of Al bound to brain ferritin has been indeed proposed as a detoxification mechanism which protects the brain metabolism from Al that cannot be cleared by other mechanisms.…”

mentioning

confidence: 99%

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Mechanism of aluminium bio-mineralization in the apoferritin cavity

Chiarpotto

Ciasca

Vassalli

et al. 2013

Applied Physics Letters

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contrasting

confidence: 51%

mentioning

confidence: 89%

mentioning

confidence: 93%

“…This mechanism could have an important role in the pathological alterations typical of this and other neurodegenerative diseases as suggested in Ref. 9.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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Mechanism of aluminium bio-mineralization in the apoferritin cavity

Chiarpotto

Ciasca

Vassalli

et al. 2013

Applied Physics Letters

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Aluminium ions in everyday life – how harmful are they?

Rößler

Heimann

2019

Chemkon

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The role of metallothionein interactions with other proteins

2014

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Metallothionein (MT) is a protein involved in numerous key processes, and the most important include zinc ion homeostasis, detoxification of heavy metals, and protection against oxidative stress. MT by interaction with other proteins fulfills its function, resulting in different effects in the body. Interaction of MT with ferritin, which causes a redox reaction, resulting in the reduction of Fe(3+) stored in ferritin and a release of harmful Fe(2+) , was observed. Referring to the redox function of MT, it has been shown that the pair of GSH/GSSG modulates transfer of Zn between MT and Zn-binding proteins. Furthermore, it was shown that GSSG, in the presence of GSH, interacts directly with MT. Apothionein-MT can retrieve Zn from the transcription factors or Zn-containing enzymes. Apothionein-MT by taking Zn can deactivate metal-dependent enzymes while Zn-MT has the opposite effect. As the effect of MT interaction with low-density lipoprotein receptors-megalin and lipoprotein receptor related protein 1, the uptake of Cd-MT occurs and results in the disruption of many functions of proximal tubules. MT is involved in numerous processes and many of them are regulated by protein-protein interactions. Possibly in the future MT will become a therapeutic agent, which will result in a breakthrough in the field of pharmacy and medicine.

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Possible relationship between Al/ferritin complex and Alzheimer's disease

Cited by 52 publications

References 28 publications

Mechanism of aluminium bio-mineralization in the apoferritin cavity

Mechanism of aluminium bio-mineralization in the apoferritin cavity

Aluminium ions in everyday life – how harmful are they?

The role of metallothionein interactions with other proteins

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