Department of Molecular Medicine, College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd, MDC07, Tampa, Florida 33612, USA.
Metallomics. 2011 Nov;3(11):1163-80. doi: 10.1039/c1mt00106j. Epub 2011 Aug 25.
Neurodegenerative diseases constitute a set of pathological conditions originating from the slow, irreversible, and systematic cell loss within the various regions of the brain and/or the spinal cord. Depending on the affected region, the outcomes of the neurodegeneration are very broad and diverse, ranging from the problems with movements to dementia. Some neurodegenerative diseases are associated with protein misfolding and aggregation. Many proteins that misfold in human neurodegenerative diseases are intrinsically disordered; i.e., they lack a stable tertiary and/or secondary structure under physiological conditions in vitro. These intrinsically disordered proteins (IDPs) functionally complement ordered proteins, being typically involved in regulation and signaling. There is accumulating evidence that altered metal homeostasis may be related to the progression of neurodegenerative diseases. This review examines the effects of metal ion binding on the aggregation pathways of IDPs found in neurodegenerative diseases.
神经退行性疾病是一组源自大脑和/或脊髓各个区域内的细胞缓慢、不可逆转和系统性丧失的病理状况。根据受影响的区域，神经退行性疾病的后果非常广泛和多样，从运动问题到痴呆症都有。一些神经退行性疾病与蛋白质错误折叠和聚集有关。在人类神经退行性疾病中错误折叠的许多蛋白质是无规卷曲的，即在体外生理条件下缺乏稳定的三级和/或二级结构。这些无规卷曲的蛋白质（IDPs）在功能上补充了有序蛋白质，通常参与调节和信号转导。越来越多的证据表明，金属离子稳态的改变可能与神经退行性疾病的进展有关。本综述考察了金属离子结合对神经退行性疾病中发现的 IDPs 聚集途径的影响。
