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Lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in MPTP-treated mice

Brain iron accumulation is common in patients with Parkinson's disease (PD). Iron chelators have been investigated for their ability to prevent neurodegenerative diseases with features of iron overload. Given the non-trivial side effects of classical iron chelators, lactoferrin (Lf), a multifun...

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Autores principales: Xu, Shuang-Feng, Zhang, Yan-Hui, Wang, Shan, Pang, Zhong-Qiu, Fan, Yong-Gang, Li, Jia-Yi, Wang, Zhan-You, Guo, Chuang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307097/
https://www.ncbi.nlm.nih.gov/pubmed/30593976
http://dx.doi.org/10.1016/j.redox.2018.101090
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author Xu, Shuang-Feng
Zhang, Yan-Hui
Wang, Shan
Pang, Zhong-Qiu
Fan, Yong-Gang
Li, Jia-Yi
Wang, Zhan-You
Guo, Chuang
author_facet Xu, Shuang-Feng
Zhang, Yan-Hui
Wang, Shan
Pang, Zhong-Qiu
Fan, Yong-Gang
Li, Jia-Yi
Wang, Zhan-You
Guo, Chuang
author_sort Xu, Shuang-Feng
collection PubMed
description Brain iron accumulation is common in patients with Parkinson's disease (PD). Iron chelators have been investigated for their ability to prevent neurodegenerative diseases with features of iron overload. Given the non-trivial side effects of classical iron chelators, lactoferrin (Lf), a multifunctional iron-binding globular glycoprotein, was screened to identify novel neuroprotective pathways against dopaminergic neuronal impairment. We found that Lf substantially ameliorated PD-like motor dysfunction in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. We further showed that Lf could alleviate MPTP-triggered apoptosis of DA neurons, neuroinflammation, and histological alterations. As expected, we also found that Lf suppressed MPTP-induced excessive iron accumulation and the upregulation of divalent metal transporter (DMT1) and transferrin receptor (TFR), which is the main intracellular iron regulation protein, and subsequently improved the activity of several antioxidant enzymes. We probed further and determined that the neuroprotection provided by Lf was involved in the upregulated levels of brain-derived neurotrophic factor (BDNF), hypoxia-inducible factor 1α (HIF-1α) and its downstream protein, accompanied by the activation of extracellular regulated protein kinases (ERK) and cAMP response element binding protein (CREB), as well as decreased phosphorylation of c-Jun N-terminal kinase (JNK) and mitogen activated protein kinase (MAPK)/P38 kinase in vitro and in vivo. Our findings suggest that Lf may be an alternative safe drug in ameliorating MPTP-induced brain abnormalities and movement disorder.
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spelling pubmed-63070972018-12-28 Lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in MPTP-treated mice Xu, Shuang-Feng Zhang, Yan-Hui Wang, Shan Pang, Zhong-Qiu Fan, Yong-Gang Li, Jia-Yi Wang, Zhan-You Guo, Chuang Redox Biol Research Paper Brain iron accumulation is common in patients with Parkinson's disease (PD). Iron chelators have been investigated for their ability to prevent neurodegenerative diseases with features of iron overload. Given the non-trivial side effects of classical iron chelators, lactoferrin (Lf), a multifunctional iron-binding globular glycoprotein, was screened to identify novel neuroprotective pathways against dopaminergic neuronal impairment. We found that Lf substantially ameliorated PD-like motor dysfunction in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. We further showed that Lf could alleviate MPTP-triggered apoptosis of DA neurons, neuroinflammation, and histological alterations. As expected, we also found that Lf suppressed MPTP-induced excessive iron accumulation and the upregulation of divalent metal transporter (DMT1) and transferrin receptor (TFR), which is the main intracellular iron regulation protein, and subsequently improved the activity of several antioxidant enzymes. We probed further and determined that the neuroprotection provided by Lf was involved in the upregulated levels of brain-derived neurotrophic factor (BDNF), hypoxia-inducible factor 1α (HIF-1α) and its downstream protein, accompanied by the activation of extracellular regulated protein kinases (ERK) and cAMP response element binding protein (CREB), as well as decreased phosphorylation of c-Jun N-terminal kinase (JNK) and mitogen activated protein kinase (MAPK)/P38 kinase in vitro and in vivo. Our findings suggest that Lf may be an alternative safe drug in ameliorating MPTP-induced brain abnormalities and movement disorder. Elsevier 2018-12-21 /pmc/articles/PMC6307097/ /pubmed/30593976 http://dx.doi.org/10.1016/j.redox.2018.101090 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Paper
Xu, Shuang-Feng
Zhang, Yan-Hui
Wang, Shan
Pang, Zhong-Qiu
Fan, Yong-Gang
Li, Jia-Yi
Wang, Zhan-You
Guo, Chuang
Lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in MPTP-treated mice
title Lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in MPTP-treated mice
title_full Lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in MPTP-treated mice
title_fullStr Lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in MPTP-treated mice
title_full_unstemmed Lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in MPTP-treated mice
title_short Lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in MPTP-treated mice
title_sort lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in mptp-treated mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307097/
https://www.ncbi.nlm.nih.gov/pubmed/30593976
http://dx.doi.org/10.1016/j.redox.2018.101090
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