细胞朊蛋白与阿尔茨海默病：与寡聚态淀粉样β和神经元细胞死亡的关联。
Cellular prion protein and Alzheimer disease: link to oligomeric amyloid-β and neuronal cell death.
机构信息
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
出版信息
Prion. 2013 Mar-Apr;7(2):114-6. doi: 10.4161/pri.22848. Epub 2012 Nov 15.
Abstract
Soluble oligomeric amyloid-β (Aβ) has been suggested to impair synaptic and neuronal function, leading to neurodegeneration that is clinically observed as the memory and cognitive dysfunction characteristic of Alzheimer disease, while the precise mechanism(s) whereby oligomeric Aβ causes neurotoxicity remains unknown. Recently, the cellular prion protein (PrP (C) ) was reported to be an essential co-factor in mediating the neurotoxic effect of oligomeric Aβ. Our recent study showed that Prnp (-/-) mice are resistant to the neurotoxic effect of oligomeric Aβ in vivo and in vitro. Furthermore, application of an anti-PrP (C) antibody or PrP (C) peptide was able to block oligomeric Aβ-induced neurotoxicity. These findings demonstrate that PrP (C) may be involved in neuropathologic conditions other than conventional prion diseases, i.e., Creutzfeldt-Jakob disease.
摘要
可溶性寡聚体淀粉样β（Aβ）被认为会损害突触和神经元功能，导致神经退行性变，临床上表现为阿尔茨海默病的记忆和认知功能障碍，而寡聚体 Aβ 引起神经毒性的确切机制尚不清楚。最近，细胞朊病毒蛋白（PrP（C））被报道为介导寡聚体 Aβ神经毒性作用的必需辅助因子。我们最近的研究表明，Prnp（-/-）小鼠在体内和体外对寡聚体 Aβ的神经毒性作用具有抗性。此外，应用抗-PrP（C）抗体或 PrP（C）肽能够阻断寡聚体 Aβ诱导的神经毒性。这些发现表明 PrP（C）可能参与除传统朊病毒病（如克雅氏病）以外的神经病理学状况。
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