Yong Shin Jie, Veerakumarasivam Abhimanyu, Lim Wei Ling, Chew Jactty
Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia.
ACS Chem Neurosci. 2023 Mar 30. doi: 10.1021/acschemneuro.2c00679.
Recent advancements in lactoferrin research have uncovered that lactoferrin does function not only as an antimicrobial protein but also as an immunomodulatory, anticancer, and neuroprotective agent. Focusing on neuroprotection, this literature review delineates how lactoferrin interacts in the brain, specifically its neuroprotective effects and mechanisms against Alzheimer's and Parkinson's diseases (AD and PD), the two most common neurodegenerative diseases. The neuroprotective pathways involving surface receptors (heparan sulfate proteoglycan (HSPG) and lactoferrin receptor (LfR)), signaling pathways (extracellular regulated protein kinase-cAMP response element-binding protein (ERK-CREB) and phosphoinositide 3-kinase/Akt (PI3K/Akt)), and effector proteins (A disintegrin and metalloprotease10 (ADAM10) and hypoxia-inducible factor 1α (HIF-1α)) in cortical/hippocampal and dopaminergic neurons are described. These cellular effects of lactoferrin are likely responsible for attenuating cognitive and motor deficits, amyloid-β and α-synuclein accumulation, and neurodegeneration in animal and cellular models of AD and PD. This review also discusses the inconsistent findings related to the neuroprotective effects of lactoferrin against AD. Overall, this review contributes to the existing literature by clarifying the potential neuroprotective effects and mechanisms of lactoferrin in the context of AD and PD neuropathology.
乳铁蛋白研究的最新进展发现,乳铁蛋白不仅具有抗菌蛋白的功能,还具有免疫调节、抗癌和神经保护作用。本文献综述聚焦于神经保护,阐述了乳铁蛋白在大脑中的相互作用方式,特别是其对两种最常见的神经退行性疾病——阿尔茨海默病和帕金森病(AD和PD)的神经保护作用及机制。文中描述了皮质/海马体和多巴胺能神经元中涉及表面受体(硫酸乙酰肝素蛋白聚糖(HSPG)和乳铁蛋白受体(LfR))、信号通路(细胞外调节蛋白激酶 - 环磷酸腺苷反应元件结合蛋白(ERK - CREB)和磷脂酰肌醇3 - 激酶/蛋白激酶B(PI3K/Akt))以及效应蛋白(解整合素和金属蛋白酶10(ADAM10)和缺氧诱导因子1α(HIF - 1α))的神经保护途径。乳铁蛋白的这些细胞效应可能是减轻AD和PD动物及细胞模型中的认知和运动缺陷、淀粉样β蛋白和α - 突触核蛋白积累以及神经退行性变的原因。本综述还讨论了与乳铁蛋白对AD的神经保护作用相关的不一致研究结果。总体而言,本综述通过阐明乳铁蛋白在AD和PD神经病理学背景下的潜在神经保护作用及机制,为现有文献做出了贡献。