Brain lactoferrin: origins and mechanisms of accumulation in neurodegenerative disorders

Abstract : Several lines of evidence indicate that alterations in iron metabolism and/or immune-mediated pathophysiology might contribute to neuronal loss. Recently, lactoferrin, an iron-binding protein and a modulatory agent of the inflammatory response, has been associated with neurodegenerative disorders. We have shown that the source of lactoferrin in brain tissues is double, either synthezised in situ or originating from the circulating blood, and we investigated the mechanisms by which lactoferrin accumulates in pathological conditions. Lactoferrin is synthezised in situ in the mouse brain. An animal model of Parkinson's disease was used to study the expression of lactoferrin in pathological conditions. Lactoferrin expression was increased after treatment with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) which is selectively toxic to the dopaminergic neurons, suggesting that lactoferrin might be produced in response to the oxidative stress generate by the neurodegenerative process occurring in Parkinson's disease. Lactoferrin crosses the blood-brain barrier (BBB). An in vitro model of the BBB was used to characterize the transport of lactoferrin through the brain capillary endothelial cells. We next showed, that this transport was increased in inflammatory conditions, leading to lactoferrin accumulation in the cerebral compartment. This accumulation may account for the increased level of lactoferrin observed in the vicinity of the inflammatory foci.
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Chapitre d'ouvrage
Lactoferrin: structure, function and applications., Elsevier, p. 67-76, 2000
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https://hal-univ-artois.archives-ouvertes.fr/hal-00552126
Contributeur : Wilfried Déplanques <>
Soumis le : mercredi 5 janvier 2011 - 15:13:36
Dernière modification le : mardi 3 juillet 2018 - 11:26:36

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  • HAL Id : hal-00552126, version 1

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Carine Fillebeen, Roméo Cecchelli, David Dexter, Monique Benaissa, Annick Pierce. Brain lactoferrin: origins and mechanisms of accumulation in neurodegenerative disorders. Lactoferrin: structure, function and applications., Elsevier, p. 67-76, 2000. 〈hal-00552126〉

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