Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, 20132, Milan, Italy.
Division of Neuroscience, San Raffaele Scientific Institute, 20132, Milan, Italy.
Adv Exp Med Biol. 2019;1173:153-177. doi: 10.1007/978-981-13-9589-5_9.
Neurodegeneration with brain iron accumulation (NBIA) is a group of seriously devastating and life-threatening rare monogenic diseases characterized by focal iron accumulation in the brain. The main symptoms of NBIA comprise progressive movement disorder, often including painful dystonia, parkinsonism, mental disability, and early death. Currently, a single established therapy is not available to reverse the progression of these debilitating disorders. The complexity of NBIA emerged from the identification of various causative genes, and up to 15 genes have been identified to date. Although the NBIA genes are involved in different cellular biochemical pathways, they show the common characteristic of generating severe iron accumulation in the basal ganglia of the patients' brains. Thus, the molecular events that lead to brain iron overload and their important roles in the pathophysiology of the diseases are not easy to identify and are poorly understood. This review summarizes the current knowledge on NBIA disorders, with a particular focus on the data describing the role of iron in the pathogenic mechanisms.
神经退行性伴脑铁沉积症（NBIA）是一组严重的、危及生命的罕见单基因疾病，其特征是大脑中出现局灶性铁沉积。NBIA 的主要症状包括进行性运动障碍，常伴有疼痛性肌张力障碍、帕金森病、精神障碍和早逝。目前，尚无单一的既定疗法可逆转这些使人衰弱的疾病的进展。NBIA 的复杂性源于各种致病基因的鉴定，迄今为止已经鉴定出了 15 个基因。尽管 NBIA 基因参与不同的细胞生化途径，但它们表现出在患者大脑基底节中产生严重铁沉积的共同特征。因此，导致脑铁过载的分子事件及其在疾病病理生理学中的重要作用不容易识别，也理解得很差。本综述总结了 NBIA 疾病的现有知识，特别关注描述铁在发病机制中作用的数据。
