阿爾茨海默氏癥患者腦細胞內(nèi)PrP與Aβ低聚物結(jié)合（圖片來源：Thomas Deerinck NCMIR/Science Photo Library）
哺乳動物的prion蛋白PrP是細胞表面的糖蛋白,與許多神經(jīng)退行性疾病有關(guān)。一般認為可溶性淀粉狀-β肽低聚物在阿爾茨海默氏癥中起中心作用的假說已被很多人接受,，但尚沒有關(guān)于Aβ低聚物影響神經(jīng)元的機制基礎(chǔ)的介紹,。
來自幾個方面的證據(jù)表明，對神經(jīng)元上的可溶性Aβ低聚物來說,，存在一種高親和力細胞表面受體,，它在阿爾茨海默氏癥病理中起中心作用，而現(xiàn)在,，細胞鋸蛋白PrPc已被發(fā)現(xiàn)是這種作用的一個候選分子,。PrP是與“脂質(zhì)筏”相關(guān)的一種胞質(zhì)膜糖蛋白，以高親和力選擇性地結(jié)合Aβ低聚物,，調(diào)控這種肽的有害效應,。這些數(shù)據(jù)提出一個可能性：PrPc -特異性藥物也許對阿爾茨海默氏癥有療效,，而且它們還表明傳染性鋸蛋白疾病與阿爾茨海默氏癥之間有一個出乎意料的聯(lián)系。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 457, 1128-1132 (26 February 2009) | doi:10.1038/nature07761
Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers
Juha Laurén1, David A. Gimbel1, Haakon B. Nygaard1, John W. Gilbert1 & Stephen M. Strittmatter1
Cellular Neuroscience, Neurodegeneration and Repair Program, Yale University School of Medicine, New Haven, Connecticut 06536, USA
Correspondence to: Stephen M. Strittmatter1 Correspondence and requests for materials should be addressed to S.M.S.
A pathological hallmark of Alzheimer's disease is an accumulation of insoluble plaque containing the amyloid-β peptide of 40–42 amino acid residues1. Prefibrillar, soluble oligomers of amyloid-β have been recognized to be early and key intermediates in Alzheimer's-disease-related synaptic dysfunction2, 3, 4, 5, 6, 7, 8, 9. At nanomolar concentrations, soluble amyloid-β oligomers block hippocampal long-term potentiation7, cause dendritic spine retraction from pyramidal cells5, 8 and impair rodent spatial memory2. Soluble amyloid- oligomers have been prepared from chemical syntheses, transfected cell culture supernatants, transgenic mouse brain and human Alzheimer's disease brain2, 4, 7, 9. Together, these data imply a high-affinity cell-surface receptor for soluble amyloid- oligomers on neurons—one that is central to the pathophysiological process in Alzheimer's disease. Here we identify the cellular prion protein (PrPc) as an amyloid-β-oligomer receptor by expression cloning. Amyloid- oligomers bind with nanomolar affinity to PrPc, but the interaction does not require the infectious PrPSc conformation. Synaptic responsiveness in hippocampal slices from young adult PrP null mice is normal, but the amyloid-β oligomer blockade of long-term potentiation is absent. Anti-PrP antibodies prevent amyloid-β-oligomer binding to PrPc and rescue synaptic plasticity in hippocampal slices from oligomeric amyloid-β. Thus, PrPc is a mediator of amyloid-β-oligomer-induced synaptic dysfunction, and PrPc-specific pharmaceuticals may have therapeutic potential for Alzheimer's disease.
