Creutzfeldt-Jakob disease (CJD) is characterized by a rapidly progressive dementia often accompanied by myoclonus and other signs of brain dysfunction, relying on the conversion of the normal cellular form of the prion protein (PrPC) to a misfolded form (PrPSc). The neuropathological changes include spongiform degeneration, neuronal loss, astrogliosis, and deposition of PrPSc. It is still unclear how these pathological changes correlate with the development of CJD symptoms because few patients survive beyond 2 years after diagnosis. Inasmuch as the symptoms of CJD overlap some of those observed in Alzheimer's, Parkinson's, and Huntington's diseases, there may be some underlying pathologic mechanisms associated with CJD that may contribute to the symptoms of non-prion neurodegenerative diseases as well. Data suggest that imbalance of metals, including copper, zinc, iron, and manganese, induces abnormalities in processing and degradation of prion proteins that are accompanied by self-propagation of PrPSc. These events appear to be responsible for glutamatergic synaptic dysfunctions, neuronal death, and PrPSc aggregation. Given that the prodromal symptoms of CJD such as sleep disturbances and mood disorders are associated with brain stem and limbic system dysfunction, the pathological changes may initially occur in these brain regions, then spread throughout the entire brain. Alterations in cerebrospinal fluid homeostasis, which may be linked to imbalance of these metals, seem to be more important than neuroinflammation in causing the cell death. It is proposed that metal dyshomeostasis could be responsible for the initiation and progression of the pathological changes associated with symptoms of CJD and other neurodegenerative disorders.

中文翻译：

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神经退行性疾病中的金属稳态紊乱，特别着重于Creutzfeldt-Jakob病-潜在的致病机理和治疗意义。

Creutzfeldt-Jakob病（CJD）的特征是快速进行性痴呆，通常伴有肌阵挛和其他脑功能障碍迹象，这取决于rely病毒蛋白（PrPC）的正常细胞形式向错误折叠形式（PrPSc）的转化。神经病理学改变包括海绵状变性，神经元丢失，星形胶质增生和PrPSc沉积。尚不清楚这些病理变化与CJD症状的发展如何相关，因为很少有患者在诊断后存活超过2年。由于CJD的症状与在阿尔茨海默氏病，帕金森氏病和亨廷顿氏病中观察到的某些症状重叠，因此与CJD相关的某些潜在病理机制也可能导致非pr病毒神经退行性疾病的症状。数据表明，金属（包括铜，锌，铁和锰）的不平衡会导致病毒蛋白的加工和降解异常，并伴有PrPSc的自我繁殖。这些事件似乎是造成谷氨酸能突触功能障碍，神经元死亡和PrPSc聚集的原因。鉴于CJD的前驱症状（如睡眠障碍和情绪障碍）与脑干和边缘系统功能障碍相关，因此病理变化可能最初发生在这些脑部区域，然后扩散到整个脑部。脑脊液稳态的改变，可能与这些金属的不平衡有关，在引起细胞死亡方面比神经炎症更重要。