近日,，波士頓大學(xué)醫(yī)學(xué)院（BUSM）研究人員確定阿爾茨海默氏癥患者大腦中一種積聚的蛋白質(zhì)組。這些調(diào)查結(jié)果發(fā)表在Journal of Neuroscience雜志上,，該研究可能有助開辟新的方法來(lái)診斷治療阿爾茨海默氏癥患者,。
β-淀粉樣蛋白聚集誘導(dǎo)神經(jīng)元蛋白質(zhì)聚集引起阿爾茨海默氏病，阿爾茨海默氏病是一種神經(jīng)退行性疾病,。阿爾茨海默氏病的診斷對(duì)象主要是β-淀粉樣蛋白和tau蛋白,，主要用放射性標(biāo)記物來(lái)結(jié)合β-淀粉樣蛋白。然而β-淀粉樣蛋白的成像是有問(wèn)題的,，因?yàn)樵S多認(rèn)知正常的老年人大腦中也有大量的β-淀粉樣蛋白,，因此檢測(cè)結(jié)果中會(huì)出現(xiàn)陽(yáng)性結(jié)果,。
近日，BUSM研究人員發(fā)現(xiàn)新的蛋白質(zhì)組稱為RNA結(jié)合蛋白,，該蛋白也在阿爾茨海默氏癥患者大腦中積累,，尤其是在那些認(rèn)知能力低于正常水平的老年人。該研究小組發(fā)現(xiàn)蛋白質(zhì)如TIA-1和TTP聚集,，誘導(dǎo)tau蛋白在神經(jīng)元聚集,。Benjamin Wolozin博士解釋說(shuō)：這些蛋白質(zhì)還結(jié)合tau，可能參與疾病的發(fā)生發(fā)展過(guò)程,。一個(gè)不同的RNA結(jié)合蛋白——G3BP聚集在神經(jīng)元中,，但不會(huì)誘導(dǎo)病理性tau蛋白聚集。
研究人員認(rèn)為這項(xiàng)工作量化這些RNA結(jié)合蛋白這一生物標(biāo)志物有利于開辟新的方法來(lái)診斷治療阿爾茨海默氏癥患者,。（生物谷：Bioon.com）
doi:10.1523/JNEUROSCI.1592-12.2012
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Contrasting Pathology of the Stress Granule Proteins TIA-1 and G3BP in Tauopathies
Tara Vanderweyde, Haung Yu, Megan Varnum, Liqun Liu-Yesucevitz, Allison Citro, Tsuneya Ikezu, Karen Duff, and Benjamin Wolozin
Stress induces aggregation of RNA-binding proteins to form inclusions, termed stress granules (SGs). Recent evidence suggests that SG proteins also colocalize with neuropathological structures, but whether this occurs in Alzheimer's disease is unknown. We examined the relationship between SG proteins and neuropathology in brain tissue from P301L Tau transgenic mice, as well as in cases of Alzheimer's disease and FTDP-17. The pattern of SG pathology differs dramatically based on the RNA-binding protein examined. SGs positive for T-cell intracellular antigen-1 (TIA-1) or tristetraprolin (TTP) initially do not colocalize with tau pathology, but then merge with tau inclusions as disease severity increases. In contrast, G3BP (ras GAP-binding protein) identifies a novel type of molecular pathology that shows increasing accumulation in neurons with increasing disease severity, but often is not associated with classic markers of tau pathology. TIA-1 and TTP both bind phospho-tau, and TIA-1 overexpression induces formation of inclusions containing phospho-tau. These data suggest that SG formation might stimulate tau pathophysiology. Thus, study of RNA-binding proteins and SG biology highlights novel pathways interacting with the pathophysiology of AD, providing potentially new avenues for identifying diseased neurons and potentially novel mechanisms regulating tau biology.
