Genetics and Pathophysiology of Neurodegeneration with Brain Iron Accumulation (NBIA).
Genetics and Pathophysiology of Neurodegeneration with Brain Iron Accumulation (NBIA).
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DOI：
10.2174/157015913804999469
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发表时间：
2013-01
影响因子：
5.3
通讯作者：
Bhatia KP
中科院分区：
文献类型：
--
作者：
Schneider SA;Dusek P;Hardy J;Westenberger A;Jankovic J;Bhatia KP
我们对神经退行性变伴脑铁蓄积(NBIA)综合征的理解继续有很大的增长。除了泛酸激酶相关的神经变性(PKAN，NBIA1)和PLA2G6相关的神经变性(PLAN，NBIA2)的核心症状外，还发现了其他几种遗传原因(包括FA2H，C19orf12，ATP13A2，CP和FTL)。与此同时，临床和病理范围扩大，新的年龄相关的表现正在被描述。人们也越来越多地认识到不同的NBIA疾病与其他疾病之间的重叠，包括痉挛性截瘫、脑白质营养不良和神经元蜡样脂褐素沉着症，这使得仅基于临床表现的诊断具有挑战性。对基因确诊病例的尸检显示，路易体、神经原纤维缠结和其他明显明显的神经退行性疾病的特征，如帕金森氏病(PD)和阿尔茨海默病。在我们解开各种NBIA基因及其相关途径并转向针对发病机制的治疗之前，治疗仍然是有症状的。我们在这里的目的是提供铁代谢研究的历史发展及其与神经退行性疾病的相关性的概述。然后，我们重点介绍NBIA的临床特征和研究结果，并总结治疗结果，回顾铁螯合疗法和脑深部刺激的报道。我们还讨论了NBIA综合征的遗传和分子基础。
Our understanding of the syndromes of Neurodegeneration with Brain Iron Accumulation (NBIA) continues to grow considerably. In addition to the core syndromes of pantothenate kinase-associated neurodegeneration (PKAN, NBIA1) and PLA2G6-associated neurodegeneration (PLAN, NBIA2), several other genetic causes have been identified (including FA2H, C19orf12, ATP13A2, CP and FTL). In parallel, the clinical and pathological spectrum has broadened and new age-dependent presentations are being described. There is also growing recognition of overlap between the different NBIA disorders and other diseases including spastic paraplegias, leukodystrophies and neuronal ceroid lipofuscinosis which makes a diagnosis solely based on clinical findings challenging. Autopsy examination of genetically-confirmed cases demonstrates Lewy bodies, neurofibrillary tangles, and other hallmarks of apparently distinct neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer’s disease. Until we disentangle the various NBIA genes and their related pathways and move towards pathogenesis-targeted therapies, the treatment remains symptomatic. Our aim here is to provide an overview of historical developments of research into iron metabolism and its relevance in neurodegenerative disorders. We then focus on clinical features and investigational findings in NBIA and summarize therapeutic results reviewing reports of iron chelation therapy and deep brain stimulation. We also discuss genetic and molecular underpinnings of the NBIA syndromes.
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影响因子：
3.8
作者：
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通讯作者：
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