以色列特拉維夫大學(xué)生理學(xué)家伊娜·斯盧特斯基博士領(lǐng)導(dǎo)的研究小組發(fā)現(xiàn),，β淀粉狀蛋白除可引發(fā)老年癡呆外,，還具有調(diào)節(jié)大腦神經(jīng)鍵間信號傳輸?shù)淖饔茫挥衅浜勘３制胶?，神?jīng)網(wǎng)絡(luò)才能正常工作,，過多或過少都可引發(fā)老年癡呆。
此前研究顯示,，β淀粉狀蛋白是一種與老年癡呆有關(guān)的有毒物質(zhì),。斯盧特斯基博士在實驗中發(fā)現(xiàn)了這種蛋白質(zhì)在大腦中發(fā)揮作用的分子機制。研究顯示,，過量β淀粉狀蛋白會導(dǎo)致神經(jīng)鍵數(shù)量下降,，影響大腦中負責(zé)學(xué)習(xí)和記憶區(qū)域的分子功能,；一旦大腦中的β淀粉狀蛋白開始大量聚集,，引發(fā)老年癡呆的過程將很難逆轉(zhuǎn),，即使將其清除也沒太大作用，因此,，必須在其大量產(chǎn)生的初期加以控制,，如等到這種蛋白質(zhì)大量聚集再采取措施就為時過晚了。
與此同時,，研究人員還驚奇地發(fā)現(xiàn),，β淀粉狀蛋白具有在健康大腦神經(jīng)間傳遞信息的重要作用，如果這種蛋白質(zhì)顯著下降,，同樣會損害分子功能,。這表明，大腦神經(jīng)網(wǎng)絡(luò)與β淀粉狀蛋白存在某種經(jīng)過優(yōu)化的平衡關(guān)系,，以確保信息的順利傳遞,，該蛋白質(zhì)太多或太少都會打破這種平衡。研究人員表示,，他們將進一步研究這一機制,，以便開發(fā)出一種防止這種蛋白質(zhì)過量聚集的藥物，而不是僅僅將其摧毀,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Neuroscience 12, 1567 - 1576 (2009) 22 November 2009 | doi:10.1038/nn.2433
Amyloid-β as a positive endogenous regulator of release probability at hippocampal synapses
Efrat Abramov1,3, Iftach Dolev1,3, Hilla Fogel1, Giuseppe D Ciccotosto2, Eyal Ruff1 & Inna Slutsky1
Accumulation of cerebral amyloid- peptide (Aβ) is essential for developing synaptic and cognitive deficits in Alzheimer's disease. However, the physiological functions of A, as well as the primary mechanisms that initiate early A-mediated synaptic dysfunctions, remain largely unknown. Here we examine the acute effects of endogenously released Aβ peptides on synaptic transfer at single presynaptic terminals and synaptic connections in rodent hippocampal cultures and slices. Increasing extracellular Aβ by inhibiting its degradation enhanced release probability, boosting ongoing activity in the hippocampal network. Presynaptic enhancement mediated by Aβ was found to depend on the history of synaptic activation, with lower impact at higher firing rates. Notably, both elevation and reduction in Aβ levels attenuated short-term synaptic facilitation during bursts in excitatory synaptic connections. These observations suggest that endogenous Aβ peptides have a crucial role in activity-dependent regulation of synaptic vesicle release and might point to the primary pathological events that lead to compensatory synapse loss in Alzheimer's disease.
1 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
2 Department of Pathology, Bio21 Molecular Science and Biotechnology Institute and Mental Health Research Institute, The University of Melbourne, Parkville, Victoria, Australia.
3 These authors contributed equally to this work.
