Institute of Brain Science and Disease, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders , Qingdao University , Qingdao , Shandong 266071 , China.
ACS Chem Neurosci. 2019 Feb 20;10(2):863-871. doi: 10.1021/acschemneuro.8b00390. Epub 2019 Jan 11.
Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc). Although both iron accumulation and a defective autophagy-lysosome pathway contribute to the pathological development of PD, the connection between these two causes is poorly documented. The autophagy-lysosome pathway not only responds to regulation by iron chelators and channels but also participates in cellular iron recycling through the degradation of ferritin and other iron-containing components. Previously, ferritin has been posited to be the bridge between iron accumulation and autophagy impairment in PD. In addition, iron directly interacts with α-synuclein in Lewy bodies, which are primarily digested through the autophagy-lysosome pathway. These findings indicate that some link exists between iron deposition and autophagy impairment in PD. In this review, the basic mechanisms of the autophagy-lysosome pathway and iron trafficking are introduced, and then their interaction under physiological conditions is explained. Finally, we finish by discussing the dysfunction of iron deposition and autophagy in PD, as well as their potential relationship, which will provide some insight for further study.
帕金森病（PD）是第二常见的神经退行性疾病，其特征是黑质致密部（SNpc）中的多巴胺能神经元丧失。尽管铁积累和自噬-溶酶体途径缺陷都有助于 PD 的病理发展，但这两个原因之间的联系还没有得到很好的记录。自噬-溶酶体途径不仅对铁螯合剂和通道的调节有反应，而且还通过降解铁蛋白和其他含铁成分参与细胞内铁的再循环。以前，铁蛋白被认为是 PD 中铁积累和自噬损伤之间的桥梁。此外，铁直接与Lewy 体中的α-突触核蛋白相互作用，Lewy 体主要通过自噬-溶酶体途径进行消化。这些发现表明 PD 中的铁沉积和自噬损伤之间存在某种联系。在这篇综述中，介绍了自噬-溶酶体途径和铁转运的基本机制，然后解释了它们在生理条件下的相互作用。最后，我们讨论了 PD 中铁沉积和自噬的功能障碍及其潜在关系，这将为进一步的研究提供一些见解。
