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一项功能异常表达筛选揭示了 Enabled 在进行性神经退行性变中的作用。

A functional misexpression screen uncovers a role for enabled in progressive neurodegeneration.

作者信息

Rezával Carolina, Berni Jimena, Gorostiza Ezequiel Axel, Werbajh Santiago, Fagilde María Marta, Fernández María Paz, Beckwith Esteban J, Aranovich Ezequiel J, Sabio y García Carmen A, Ceriani María Fernanda

机构信息

Laboratorio de Genética del Comportamiento, Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas-Buenos Aires (IIB-BA, CONICET), Buenos Aires, Argentina.

出版信息

PLoS One. 2008 Oct 8;3(10):e3332. doi: 10.1371/journal.pone.0003332.

DOI:10.1371/journal.pone.0003332
PMID:18841196
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2553195/
Abstract

Drosophila is a well-established model to study the molecular basis of neurodegenerative diseases. We carried out a misexpression screen to identify genes involved in neurodegeneration examining locomotor behavior in young and aged flies. We hypothesized that a progressive loss of rhythmic activity could reveal novel genes involved in neurodegenerative mechanisms. One of the interesting candidates showing progressive arrhythmicity has reduced enabled (ena) levels. ena down-regulation gave rise to progressive vacuolization in specific regions of the adult brain. Abnormal staining of pre-synaptic markers such as cystein string protein (CSP) suggest that axonal transport could underlie the neurodegeneration observed in the mutant. Reduced ena levels correlated with increased apoptosis, which could be rescued in the presence of p35, a general Caspase inhibitor. Thus, this mutant recapitulates two important features of human neurodegenerative diseases, i.e., vulnerability of certain neuronal populations and progressive degeneration, offering a unique scenario in which to unravel the specific mechanisms in an easily tractable organism.

摘要

果蝇是研究神经退行性疾病分子基础的成熟模型。我们进行了一项错误表达筛选，通过检测年轻和老年果蝇的运动行为来鉴定参与神经退行性变的基因。我们假设节律性活动的逐渐丧失可能揭示参与神经退行性机制的新基因。其中一个表现出逐渐心律失常的有趣候选基因是 Enabled（ena）水平降低。ena 下调导致成年大脑特定区域出现渐进性空泡化。突触前标记物如半胱氨酸串蛋白（CSP）的异常染色表明轴突运输可能是突变体中观察到的神经退行性变的基础。ena 水平降低与细胞凋亡增加相关，在存在一般半胱天冬酶抑制剂 p35 的情况下这种情况可以得到挽救。因此，这个突变体重现了人类神经退行性疾病的两个重要特征，即某些神经元群体的易损性和进行性退化，为在易于处理的生物体中揭示具体机制提供了独特的情境。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/f1faa64623b7/pone.0003332.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/c3c9382dce54/pone.0003332.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/14ec19c899f0/pone.0003332.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/098bb2ef8d0c/pone.0003332.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/ed9980920719/pone.0003332.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/bbb20a4acbca/pone.0003332.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/b6577561d3b1/pone.0003332.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/f1faa64623b7/pone.0003332.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/c3c9382dce54/pone.0003332.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/14ec19c899f0/pone.0003332.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/098bb2ef8d0c/pone.0003332.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/ed9980920719/pone.0003332.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/bbb20a4acbca/pone.0003332.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/b6577561d3b1/pone.0003332.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/142e/2553195/f1faa64623b7/pone.0003332.g007.jpg

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Filopodia are required for cortical neurite initiation.丝状伪足是皮质神经元轴突起始所必需的。
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