脑铁蓄积性神经退行性变：线粒体失调的见解。

Neurodegeneration with brain iron accumulation: Insights into the mitochondria dysregulation.

机构信息

Departments of Clinical Pharmacology and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, PR China; Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, PR China.

Department of Orthopaedics, The First Affiliated Hospital of the University of South China, Hengyang 421001, PR China.

出版信息

Biomed Pharmacother. 2019 Oct;118:109068. doi: 10.1016/j.biopha.2019.109068. Epub 2019 Aug 9.

DOI:10.1016/j.biopha.2019.109068

PMID:31404774

Abstract

NBIA (Neurodegeneration with brain iron accumulation) is a group of inherited neurologic disorders characterized by marked genetic heterogeneity, in which iron atypical accumulates in basal ganglia resulting in brain magnetic resonance imaging changes, histopathological abnormalities, and neuropsychiatric clinical symptoms. With the rapid development of high-throughput sequencing technologies, ten candidate genes have been identified, including PANK2, PLA2G6, C19orf12, WDR45, FA2H, ATP13A2, FTL, CP, C2orf37, and COASY. They are involved in seemingly unrelated cellular pathways, such as iron homeostasis (FTL, CP), lipid metabolism (PLA2G6, C19orf12, FA2H), Coenzyme A synthesis (PANK2, COASY), and autophagy (WDR45, ATP13A2). In particular, PANK2, COASY, PLA2G6, and C19orf12 are located on mitochondria, which associate with certain subtypes of NBIA showing mitochondria dysregulation. However, the relationships among those four genes are still unclear. Therefore, this review is specifically focused on dysregulation of mitochondria in NBIA and afore-mentioned four genes, with summaries of both pathological and clinical findings.

摘要

NBIA（脑铁沉积神经变性）是一组具有明显遗传异质性的遗传性神经退行性疾病，其特征是铁异常沉积在基底节，导致脑磁共振成像改变、组织病理学异常和神经精神临床症状。随着高通量测序技术的快速发展，已经确定了 10 个候选基因，包括 PANK2、PLA2G6、C19orf12、WDR45、FA2H、ATP13A2、FTL、CP、C2orf37 和 COASY。它们涉及看似不相关的细胞途径，如铁稳态（FTL、CP）、脂质代谢（PLA2G6、C19orf12、FA2H）、辅酶 A 合成（PANK2、COASY）和自噬（WDR45、ATP13A2）。特别是 PANK2、COASY、PLA2G6 和 C19orf12 位于线粒体上，与某些 NBIA 亚型的线粒体失调有关。然而，这四个基因之间的关系尚不清楚。因此，本综述特别关注 NBIA 中线粒体和上述四个基因的失调，总结了它们的病理和临床发现。