生物谷報道：近日,，拜爾醫(yī)學(xué)院（BCM）的研究人員發(fā)表在“生物科學(xué)圖書館”在線版上的一篇報道聲稱：存在于果蠅和小鼠體內(nèi)的一種稱為煙酞胺核昔酸腺昔酞基轉(zhuǎn)移酶(NMNAT) 的蛋白質(zhì)可防止神經(jīng)細(xì)胞退化,。本文的高級作者、BCM發(fā)育生物學(xué)主任和霍華德•休斯醫(yī)學(xué)研究所研究人員Hugo Bellen博士認(rèn)為,，此研究工作得賜于以下爭論：即是否可以研制可刺激產(chǎn)生另外的蛋白產(chǎn)物從而保護導(dǎo)致疾病的退化或損傷的神經(jīng)細(xì)胞,。本研究重要之處在于證明了NMNAT是機體神經(jīng)元生存所必需的重要因素。本文的大部分工作是由第一作者,、Bellen實驗室的博士后――來自中國的R. Grace Zhai完成,。
五年前，科學(xué)家發(fā)現(xiàn)小鼠含有一個基因的三個拷貝,，其中含有NMNAT和另一種蛋白質(zhì),。Bellen和同事在果蠅和黑腹果蠅（一種常用的模式動物）體內(nèi)研究NMNAT的突變體來觀察NMNAT的神經(jīng)保護作用。NMNAT單體只存在于果蠅,，而且只有一種形式,。
當(dāng)Zhai、Bellen和同事們發(fā)現(xiàn)神經(jīng)系統(tǒng)缺失蛋白的果蠅的神經(jīng)元退化迅速,，但是將他們放在暗處可降低退化過程并避免激活視神經(jīng)元,。若缺乏NMNAT蛋白，眼中的感光器發(fā)育正常,，他們會伸出軸突（將神經(jīng)卷曲延伸生長進入腦組織）和形成突觸（具有連接神經(jīng)軸突和靶細(xì)胞的功能）,。但是在眼發(fā)育后期，昆蟲在蛹期就可以感光,。一旦神經(jīng)元被激活,，他們就會快速退化。在出生后兩周就幾乎沒有神經(jīng)元幸存,。當(dāng)果蠅在暗處飼養(yǎng),，相對于他們曝光于亮處神經(jīng)元死亡還是很緩慢的。所以光激活顯然是細(xì)胞大量變性的原因,。當(dāng)這些果蠅眼中有大量的NMNAT產(chǎn)生,，然后在陽光下放置30天。他們發(fā)現(xiàn)只有20%的神經(jīng)元死亡,，這說明此蛋白對維持神經(jīng)元的生存所必需的所在,，此蛋白大量存在下可延緩神經(jīng)退化過程。他們還發(fā)現(xiàn)不需要小鼠和脊椎動物的其他酶的幫助,、只在NMNAT單獨存在下就足以保護神經(jīng)元,。
Figure 1.Mutations in Complementation Group 3R4 Disrupt Synaptic Structures in Photoreceptor Terminals
(A–F) External morphology of the homozygous eyes of 3R41 (C) and 3R42 (E) are normal when compared to those of isogenized control (A). Red eye color marks heterozygous patches. (B), (D), and (F) ERG recordings of control and mutant eyes. Note the reduced depolarization and on/off response. Bar above trace in (B) indicates duration of light stimulus.
(G–I) TEM micrographs of lamina cartridges containing control, 3R41, and 3R42 mutant terminals, respectively. Demarcating glia are colored blue and photoreceptor terminals green to accentuate the structures. Note the photoreceptor terminals are disorganized in mutants. The yellow boxes in (G) and (I) indicate the regions shown in (J) and (K), respectively. The red boxes in (G) and (H) indicate the regions shown in (L) and (M), respectively. Scale bar in (G) for (G–I) indicates 1 μm.
(J) and (K) Individual terminals that are boxed in (G) and (I) (yellow boxes). nmnat mutant terminals have amorphic active zone structures (red arrows), aberrant capitate projections (blue arrows), aberrant mitochondria (yellow arrowheads), and abnormal membranes (yellow arrow), as well as an aberrant cytoskeleton (blue arrowheads), which are not observed in wild-type terminals. Scale bar indicates 200 nm.
(L) and (M) Individual active zones that are boxed in (G) and (H) (red boxes). Compared to the clearly defined wild-type active zone structure (L), nmnat mutant active zones are amorphic and reduced in size. Both wild-type and mutant T-bars are surrounded by synaptic vesicles. Scale bar indicates 200 nm.
(N) and (O) Quantification of synapse number and size. No significant difference was found in the average number of active zones per terminal between control (118 terminals counted), and 3R41 (93 terminals counted) or 3R42 (71 terminals counted). Synapse size was measured by the width of T-bar platform profile (L) (insert). The size of T-bars in either 3R41 (23 measured) or 3R42 (31 measured) is significantly reduced compared to the control (38 measured). An asterisk (*) indicates p < 0.05.
原文下載：
PLoS Biol. 2006 Nov 28;4(12):e416
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相關(guān)基因 Pubmed Gene
Nmnat
Nicotinamide mononucleotide adenylytran
