德州大學(xué)西南醫(yī)療中心的研究人員在一項(xiàng)動(dòng)物實(shí)驗(yàn)中發(fā)現(xiàn),，一種被認(rèn)為是老年癡呆疾病“罪魁禍?zhǔn)?rdquo;的小蛋白，其作用能夠被其他的腦蛋白抵消,。
這項(xiàng)研究結(jié)果發(fā)表在Proceedings of the National Academy of Sciences雜志上,，為抵抗這種疾病提供了一個(gè)有前途的新方法。
研究人員介紹說,，大腦中這種有害的蛋白,，叫beta-amyloid，當(dāng)其執(zhí)行正確的功能時(shí),，能夠抑制與記憶和學(xué)習(xí)有關(guān)的神經(jīng)元活性,。這就相當(dāng)于一個(gè)交通紅綠燈，當(dāng)神經(jīng)元從相鄰細(xì)胞接收到刺激信號(hào)時(shí)該蛋白會(huì)抑制神經(jīng)細(xì)胞以免其過于活躍,。然而由于老年癡呆患者大腦過多的beta-amyloid堆積,，神經(jīng)細(xì)胞變得不是很敏感。
另外還有一個(gè)大腦蛋白叫Reelin,，其就像交通綠燈,，能使神經(jīng)細(xì)胞對(duì)相鄰細(xì)胞的信號(hào)更加敏感,。
研究人員將Reelin直接作用到切割自老鼠的大腦，結(jié)果發(fā)現(xiàn),，其抵消了過多的beta-amyloid對(duì)神經(jīng)細(xì)胞的完全沉默,。
在這項(xiàng)研究中，研究人員記錄了老鼠海馬體中的電流,。海馬體是一個(gè)與學(xué)習(xí)和記憶有關(guān)的大腦區(qū)域,。從試驗(yàn)中，他們發(fā)現(xiàn)Reelin和beta-amyloid與同樣的蛋白質(zhì)塊互作,。該蛋白塊叫NMDA受體,，其在協(xié)調(diào)相鄰細(xì)胞的化學(xué)信號(hào)方面承擔(dān)了重要的作用。他們發(fā)現(xiàn)Reelin激活則對(duì)NMDA受體的應(yīng)答增強(qiáng),。過多的beta-amyloid存在時(shí),，受體會(huì)移入細(xì)胞，降低了細(xì)胞對(duì)信號(hào)的敏感性,。相反,，在Reelin集中的地方，受體仍然處于活性狀態(tài),，使細(xì)胞能夠不斷的接收刺激信號(hào),。
Herz博士介紹說，這項(xiàng)研究尤其重要,，因?yàn)檫@種機(jī)制還包括另外一個(gè)蛋白即ApoE4,，其是目前常見的神經(jīng)性疾病的首要風(fēng)險(xiǎn)因子。受體綁定ApeE分子時(shí)同樣也會(huì)綁定Reelin,，這是細(xì)胞“紅綠燈”復(fù)合物的一個(gè)部分，能夠控制NMDA受體的敏感性,。
這項(xiàng)研究結(jié)果表明,，Reelin,ApoE和beta-amyloid趨于相同的分子機(jī)制，對(duì)老年癡呆疾病的發(fā)展起著決定性作用,。該研究也為“ApoE受體具有抑制老年癡呆疾病發(fā)展的作用”這一理論建立了依據(jù),。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS September 2, 2009, doi: 10.1073/pnas.0908176106
Reelin signaling antagonizes β-amyloid at the synapse
Murat S. Durakoglugila, Ying Chena, Charles L. Whiteb, Ege T. Kavalalic and Joachim Herza,c,1
Communicated by Michael S. Brown, The University of Texas Southwestern Medical Center, Dallas, TX, July 30, 2009
Abnormal processing of the amyloid precursor protein (APP) and β-amyloid (Aβ) plaque accumulation are defining features of Alzheimer disease (AD), a genetically complex neurodegenerative disease that is characterized by progressive synapse loss and neuronal cell death. Aβ induces synaptic dysfunction in part by altering the endocytosis and trafficking of AMPA and NMDA receptors. Reelin is a neuromodulator that increases glutamatergic neurotransmission by signaling through the postsynaptic ApoE receptors Apoer2 and Vldlr and thereby potently enhances synaptic plasticity. Here we show that Reelin can prevent the suppression of long-term potentiation and NMDA receptors, which is induced by levels of Aβ comparable to those present in an AD-afflicted brain. This reversal is dependent upon the activation of Src family tyrosine kinases. At high concentrations of Aβ peptides, Reelin can no longer overcome the Aβ induced functional suppression and this coincides with a complete blockade of the Reelin-dependent phosphorylation of NR2 subunits. We propose a model in which Aβ, Reelin, and ApoE receptors modulate neurotransmission and thus synaptic stability as opposing regulators of synaptic gain control.
