Lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in MPTP-treated mice
Shuang-Feng Xu, Yan-Hui Zhang, Shan Wang, Zhong-Qiu Pang, Yong-Gang Fan, Jia-Yi Li, Zhan-You Wang, Chuang Guo
Redox Biology
Volume 21, February 2019, 101090
https://doi.org/10.1016/j.redox.2018.101090

Abstract
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.

https://www.sciencedirect.com/science/article/pii/S2213231718312084?dgcid=rss_sd_all

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