Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets.
Fetal Alcohol Spectrum Disorder (FASD) Associated Neural Defects: Complex Mechanisms and Potential Therapeutic Targets.
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DOI：
10.3390/brainsci3020964
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发表时间：
2013-06-19
期刊：
影响因子：
3.3
通讯作者：
Marrs JA
中科院分区：
文献类型：
--
作者：
Muralidharan P;Sarmah S;Zhou FC;Marrs JA
胎儿酒精谱系障碍（FASD），由产前酒精暴露引起，可导致颅面畸形，认知障碍，感觉和运动障碍等缺陷。在美国出生的儿童中，FASD的发病率高达2%至5%，并且在低社会经济水平的人群中患病率更高。尽管提出了各种机制来解释FASD的病因，但发育过程中乙醇毒性的分子靶点尚不清楚。提出的机制包括细胞死亡、细胞信号传导缺陷和基因表达变化。最近，研究人员探索了其他几种分子途径的参与，包括非编码RNA、表观遗传变化和特定维生素缺乏症。这些不同的途径可能相互作用，产生广泛的后果。对这些不同途径及其相互作用的详细了解将有助于治疗靶点的识别，从而导致新的临床干预，这可能会降低这些高度流行的可预防出生缺陷的发生率和严重程度。这篇综述讨论了酒精暴露对发育中的中枢神经系统的表现，包括神经嵴细胞和感觉神经基板，重点是分子神经发育途径作为预防或保护的可能治疗靶点。
Fetal alcohol spectrum disorder (FASD), caused by prenatal alcohol exposure, can result in craniofacial dysmorphism, cognitive impairment, sensory and motor disabilities among other defects. FASD incidences are as high as 2% to 5 % children born in the US, and prevalence is higher in low socioeconomic populations. Despite various mechanisms being proposed to explain the etiology of FASD, the molecular targets of ethanol toxicity during development are unknown. Proposed mechanisms include cell death, cell signaling defects and gene expression changes. More recently, the involvement of several other molecular pathways was explored, including non-coding RNA, epigenetic changes and specific vitamin deficiencies. These various pathways may interact, producing a wide spectrum of consequences. Detailed understanding of these various pathways and their interactions will facilitate the therapeutic target identification, leading to new clinical intervention, which may reduce the incidence and severity of these highly prevalent preventable birth defects. This review discusses manifestations of alcohol exposure on the developing central nervous system, including the neural crest cells and sensory neural placodes, focusing on molecular neurodevelopmental pathways as possible therapeutic targets for prevention or protection.