Why Is N-Glycolylneuraminic Acid Rare in the Vertebrate Brain?
Why Is N-Glycolylneuraminic Acid Rare in the Vertebrate Brain?
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DOI：
10.1007/128_2013_419
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发表时间：
2015
影响因子：
8.6
通讯作者：
Varki, Ajit
中科院分区：
文献类型：
--
作者：
Davies, Leela R. L.;Varki, Ajit
唾液酸n -乙酰神经氨酸（Neu5Ac）和n -糖基神经氨酸（Neu5Gc）只差一个氧原子，广泛存在于脊椎动物细胞表面聚糖的末端位置。在能够合成Neu5Gc的动物中，大多数组织和细胞类型都表达这两种唾液酸，其比例因物种而异。然而，人们早就注意到，迄今为止所研究的所有脊椎动物的大脑中，Neu5Gc一直以微量或缺失的水平表达。尽管有几篇报道声称在神经组织中发现了低水平的含有neu5gc的聚糖，但没有一项研究明确排除了非神经细胞类型的聚糖污染的可能性。据我们所知，这种分子的分布是独一无二的，它在神经外组织中表达得很明显，但变化很大，但在大脑中却很少或不存在。Neu5Gc的进化保守性脑特异性抑制可能表明其存在对该器官具有毒性；然而，迄今为止还没有研究直接解决这个非常有趣的问题。在此，我们提供了这一问题的历史背景，并讨论了导致Neu5Gc在脑组织中表达抑制的潜在机制，以及Neu5Gc可能发挥假定毒性的机制。最后，我们讨论了理解这一不寻常发现的机制和含义的未来方法。
The sialic acids N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) differ by a single oxygen atom and are widely found at the terminal position of glycans on vertebrate cell surfaces. In animals capable of synthesizing Neu5Gc, most tissues and cell types express both sialic acids, in proportions that vary between species. However, it has long been noted that Neu5Gc is consistently expressed at trace to absent levels in the brains of all vertebrates studied to date. Although several reports have claimed to find low levels of Neu5Gc-containing glycans in neural tissue, no study definitively excludes the possibility of contamination with glycans from non-neural cell types. This distribution of a molecule – prominently but variably expressed in extraneural tissues but very low or absent in the brain – is, to our knowledge, unique. The evolutionarily conserved brain-specific suppression of Neu5Gc may indicate that its presence is toxic to this organ; however, no studies to date have directly addressed this very interesting question. Here we provide a historical background to this issue and discuss potential mechanisms causing the suppression of Neu5Gc expression in brain tissue, as well as mechanisms by which Neu5Gc may exert the presumed toxicity. Finally, we discuss future approaches towards understanding the mechanisms and implications of this unusual finding.
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