Whole transcriptome analysis of a reversible neurodegenerative process in Drosophila reveals potential neuroprotective genes.
Whole transcriptome analysis of a reversible neurodegenerative process in Drosophila reveals potential neuroprotective genes.
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DOI：
10.1186/1471-2164-13-483
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发表时间：
2012-09-15
期刊：
影响因子：
4.4
通讯作者：
Cantera R
中科院分区：
文献类型：
--
作者：
Ferreiro MJ;Rodríguez-Ezpeleta N;Pérez C;Hackenberg M;Aransay AM;Barrio R;Cantera R
神经退行性疾病是进行性和不可逆的，它们可以由特定基因的突变引发。Spalt样基因（萨尔）编码在中枢神经系统中表达的转录因子。在人类中，萨尔突变与以智力迟钝、感觉神经性耳聋和运动神经元问题等为特征的遗传综合征相关。果蝇萨尔突变体在胚胎期16表现出严重的中枢神经系统神经变性，这在胚胎期17的发育后期令人惊讶地恢复，表明有可能从神经变性中恢复。我们假设这种恢复是由转录组的重组介导的，从而抵消了萨尔的丢失。为了鉴定与神经变性和神经保护相关的基因，我们使用mRNA-Seq比较了果蝇萨尔突变体和野生型胚胎在神经变性和逆转阶段的转录组。神经变性阶段与220个基因的转录变化相关，其中只有5%已经被描述为与神经变性相关。与氧化还原、寿命/衰老和线粒体疾病组相关的基因在此阶段有显著代表性。相反，神经退行性变逆转阶段与480个基因的显著变化相关，包括424个先前与神经保护无关的基因。免疫反应和盐胁迫是这一阶段最具代表性的群体。我们通过使用mRNA-Seq方法鉴定了与神经变性和神经保护相关的新基因。果蝇和人类基因之间的高度同源性提高了揭示涉及人类神经变性和神经保护的新基因的可能性。
Neurodegenerative diseases are progressive and irreversible and they can be initiated by mutations in specific genes. Spalt-like genes (Sall) encode transcription factors expressed in the central nervous system. In humans, SALL mutations are associated with hereditary syndromes characterized by mental retardation, sensorineural deafness and motoneuron problems, among others. Drosophila sall mutants exhibit severe neurodegeneration of the central nervous system at embryonic stage 16, which surprisingly reverts later in development at embryonic stage 17, suggesting a potential to recover from neurodegeneration. We hypothesize that this recovery is mediated by a reorganization of the transcriptome counteracting SALL lost. To identify genes associated to neurodegeneration and neuroprotection, we used mRNA-Seq to compare the transcriptome of Drosophila sall mutant and wild type embryos from neurodegeneration and reversal stages. Neurodegeneration stage is associated with transcriptional changes in 220 genes, of which only 5% were already described as relevant for neurodegeneration. Genes related to the groups of Redox, Lifespan/Aging and Mitochondrial diseases are significantly represented at this stage. By contrast, neurodegeneration reversal stage is associated with significant changes in 480 genes, including 424 not previously associated with neuroprotection. Immune response and Salt stress are the most represented groups at this stage. We identify new genes associated to neurodegeneration and neuroprotection by using an mRNA-Seq approach. The strong homology between Drosophila and human genes raises the possibility to unveil novel genes involved in neurodegeneration and neuroprotection also in humans.
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影响因子：
--
作者：
Blanco E;Ruiz-Romero M;Beltran S;Bosch M;Punset A;Serras F;Corominas M
通讯作者：
Corominas M
影响因子：
12.3
作者：
Curtis C;Landis GN;Folk D;Wehr NB;Hoe N;Waskar M;Abdueva D;Skvortsov D;Ford D;Luu A;Badrinath A;Levine RL;Bradley TJ;Tavaré S;Tower J
通讯作者：
Tower J
DOI：
10.1073/pnas.152330499
发表时间：
2002-12-10
影响因子：
11.1
作者：
Bonini, NM
通讯作者：
Bonini, NM
影响因子：
7.4
作者：
Boyd, Olga;Weng, Peter;Zou, Sige
通讯作者：
Zou, Sige
影响因子：
9.8
作者：
Al-Baradie, R;Yamada, K;Engle, EC
通讯作者：
Engle, EC