Familial Dysautonomia: Mechanisms and Models.
Familial Dysautonomia: Mechanisms and Models.
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DOI：
10.1590/1678-4685-gmb-2015-0335
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发表时间：
2016-10
影响因子：
2.1
通讯作者：
Dragatsis I
中科院分区：
文献类型：
--
作者：
Dietrich P;Dragatsis I
遗传性感觉和自主神经病（HSAN）是一组以感觉和自主神经功能障碍为特征的遗传性疾病。家族性自主神经功能障碍（FD），也称为HSAN III，是一种常染色体隐性遗传疾病，影响德系犹太人人口中1/3，600的活产婴儿。这种疾病的主要特征在出生时就已经存在，并归因于感觉和自主神经系统的异常发育和进行性退化。尽管有临床干预措施，但这种疾病不可避免地是致命的。FD是由IKBKAP基因内含子20中的点突变引起的，该点突变导致其编码蛋白IKAP的表达严重减少。体外和体内研究表明，IKAP参与多个细胞内过程，并表明，失败的目标神经支配和/或受损的神经营养逆行运输是FD中神经元细胞死亡的主要原因。然而，FD要复杂得多，除了周围神经系统外，它似乎还会影响其他几个器官和系统。随着最近一代的小鼠模型，概括了疾病的分子和病理学特征，现在有可能进一步研究疾病的不同方面的机制，并测试新的治疗策略。
Hereditary Sensory and Autonomic Neuropathies (HSANs) compose a heterogeneous group of genetic disorders characterized by sensory and autonomic dysfunctions. Familial Dysautonomia (FD), also known as HSAN III, is an autosomal recessive disorder that affects 1/3,600 live births in the Ashkenazi Jewish population. The major features of the disease are already present at birth and are attributed to abnormal development and progressive degeneration of the sensory and autonomic nervous systems. Despite clinical interventions, the disease is inevitably fatal. FD is caused by a point mutation in intron 20 of the IKBKAP gene that results in severe reduction in expression of IKAP, its encoded protein. In vitro and in vivo studies have shown that IKAP is involved in multiple intracellular processes, and suggest that failed target innervation and/or impaired neurotrophic retrograde transport are the primary causes of neuronal cell death in FD. However, FD is far more complex, and appears to affect several other organs and systems in addition to the peripheral nervous system. With the recent generation of mouse models that recapitulate the molecular and pathological features of the disease, it is now possible to further investigate the mechanisms underlying different aspects of the disorder, and to test novel therapeutic strategies.