Barros Caroline A, Vieira Tuane C R G
Institute of Medical Biochemistry Leopoldo de Meis, National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro 21941-599, RJ, Brazil.
Brain Sci. 2025 Apr 6;15(4):380. doi: 10.3390/brainsci15040380.
Lactoferrin (Lf) is a multifunctional glycoprotein with well-established antimicrobial, anti-inflammatory, and iron-binding properties. Emerging evidence suggests that Lf also plays a neuroprotective role, particularly in neurodegenerative disorders characterized by protein aggregation, such as Parkinson's disease (PD). Alpha-synuclein (aSyn) aggregation is a pathological hallmark of PD and other synucleinopathies, contributing to neuronal dysfunction and disease progression. Recent studies indicate that Lf may interfere with aSyn aggregation, iron chelation, and modulation of oxidative stress and neuroinflammation. Additionally, Lf's ability to cross the blood-brain barrier and its potential impact on the gut-brain axis highlight its promise as a therapeutic agent. This review explores Lf's mechanisms of action in synucleinopathies, its potential as a disease-modifying therapy, and innovative delivery strategies that could enhance its clinical applicability. By addressing the pathological and therapeutic dimensions of aSyn aggregation, we propose Lf as a compelling candidate for future research and clinical development in neurodegenerative diseases.
乳铁蛋白(Lf)是一种多功能糖蛋白,具有公认的抗菌、抗炎和铁结合特性。新出现的证据表明,Lf还发挥神经保护作用,尤其是在以蛋白质聚集为特征的神经退行性疾病中,如帕金森病(PD)。α-突触核蛋白(aSyn)聚集是PD和其他突触核蛋白病的病理标志,导致神经元功能障碍和疾病进展。最近的研究表明,Lf可能会干扰aSyn聚集、铁螯合以及氧化应激和神经炎症的调节。此外,Lf穿过血脑屏障的能力及其对肠脑轴的潜在影响突出了其作为治疗剂的前景。这篇综述探讨了Lf在突触核蛋白病中的作用机制、其作为疾病修饰疗法的潜力以及可增强其临床适用性的创新递送策略。通过阐述aSyn聚集的病理和治疗方面,我们提出Lf是神经退行性疾病未来研究和临床开发的一个有吸引力的候选物。