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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Shuang Feng Xu
  • Yan Hui Zhang
  • Shan Wang
  • Zhong Qiu Pang
  • Yong Gang Fan
  • Jia Yi Li
  • Zhan You Wang
  • Chuang Guo
Organisations
External organisations
  • Northeastern University
  • China Medical University, Shenyang
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • Iron chelators, Lactoferrin, Motor dysfunction, Parkinson's disease
Original languageEnglish
Article number101090
JournalRedox Biology
Volume21
Publication statusPublished - 2019 Feb 1
Publication categoryResearch
Peer-reviewedYes