Lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in MPTP-treated mice
Lactoferrin ameliorates dopaminergic neurodegeneration and motor deficits in MPTP-treated mice
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乳铁蛋白可改善 MPTP 治疗小鼠的多巴胺能神经变性和运动缺陷
DOI：
10.1016/j.redox.2018.101090
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发表时间：
2018-12
期刊：
影响因子：
11.4
通讯作者：
Guo Chuang
中科院分区：
文献类型：
--
作者：
Xu Shuang-Feng;Zhang Yan-Hui;Wang Shan;Pang Zhong-Qiu;Fan Yong-Gang;Li Jia-Yi;Wang Zhan-You;Guo Chuang
帕金森氏病(PD)患者的脑铁蓄积是很常见的。铁络合剂因其预防神经退行性疾病的能力而受到研究，这些疾病具有铁超载的特点。鉴于经典铁络合剂的副作用不小，我们筛选了一种多功能铁结合球状糖蛋白乳铁蛋白(LF)，以确定对抗多巴胺能神经元损伤的新的神经保护途径。我们发现，在亚急性1-甲基-4-苯基-1，2，3，6-四氢吡啶(MPTP)诱导的帕金森病小鼠模型中，LF显著改善了帕金森病样运动功能障碍。我们进一步表明，LF可以减轻MPTP引发的DA神经元的凋亡、神经炎症和组织学改变。正如我们所预期的那样，我们还发现，LF抑制了MPTP诱导的过量铁积累和细胞内主要铁调节蛋白二价金属转运体(DMT1)和转铁蛋白受体(TFR)的上调，从而提高了几种抗氧化酶的活性。我们进一步探讨和确定了LF的神经保护作用与其上调脑源性神经营养因子、缺氧诱导因子1α及其下游蛋白水平、激活细胞外调节蛋白激酶和cAMP反应元件结合蛋白、降低体内外c-jun氨基末端激酶和丝裂原活化蛋白激酶/P38激酶的磷酸化有关。我们的研究结果表明，LF可能是一种安全的替代药物，可以改善MPTP所致的脑异常和运动障碍。
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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影响因子：
3.3
作者：
Bae, Jung-Woo;Kim, Mi-Jeong;Lee, Seok-Yong
通讯作者：
Lee, Seok-Yong
DOI：
10.1016/j.biopha.2017.10.121
发表时间：
2018
期刊：
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
影响因子：
--
作者：
Khoo Miew Leng;S. Vijayarathna;S. L. Jothy;S. Sasidharan;J. Kanwar
通讯作者：
Khoo Miew Leng;S. Vijayarathna;S. L. Jothy;S. Sasidharan;J. Kanwar
影响因子：
4.6
作者：
J. L. Hamilton;Muhammad Imran ul-haq;A. Creagh;C. Haynes;J. Kizhakkedathu
通讯作者：
J. L. Hamilton;Muhammad Imran ul-haq;A. Creagh;C. Haynes;J. Kizhakkedathu
影响因子：
3.5
作者：
J. Shumake;Douglas W. Barrett;M. Lane;A. Wittke
通讯作者：
J. Shumake;Douglas W. Barrett;M. Lane;A. Wittke
影响因子：
3.5
作者：
E. Zakharova;Alex Sokolov;N. Pavlichenko;V. Kostevich;I. Abdurasulova;A. Chechushkov;Irina V. Voynova;A. Elizarova;N. N. Kolmakov-N.;M. G. Bass;Igor Semak;A. Budevich;P. Kozhin;N. Zenkov;V. Klimenko;O. V. Kirik;D. Korzhevskii;E. Menshchikova;V. Vasilyev
通讯作者：
E. Zakharova;Alex Sokolov;N. Pavlichenko;V. Kostevich;I. Abdurasulova;A. Chechushkov;Irina V. Voynova;A. Elizarova;N. N. Kolmakov-N.;M. G. Bass;Igor Semak;A. Budevich;P. Kozhin;N. Zenkov;V. Klimenko;O. V. Kirik;D. Korzhevskii;E. Menshchikova;V. Vasilyev