预防β-淀粉样蛋白纤维化和沉积：β-折叠破坏剂和病理性伴侣蛋白抑制剂。
Preventing beta-amyloid fibrillization and deposition: beta-sheet breakers and pathological chaperone inhibitors.
作者信息
Wisniewski Thomas, Sadowski Martin
机构信息
Department of Neurology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
出版信息
BMC Neurosci. 2008 Dec 3;9 Suppl 2(Suppl 2):S5. doi: 10.1186/1471-2202-9-S2-S5.
Abstract
Central to the pathogenesis of Alzheimer's disease (AD) is the conversion of normal, soluble beta-amyloid (sAbeta) to oligomeric, fibrillar Abeta. This process of conformational conversion can be influenced by interactions with other proteins that can stabilize the disease-associated state; these proteins have been termed 'pathological chaperones'. In a number of AD models, intervention that block soluble Abeta aggregation, including beta-sheet breakers, and compounds that block interactions with pathological chaperones, have been shown to be highly effective. When combined with early pathology detection, these therapeutic strategies hold great promise as effective and relatively toxicity free methods of preventing AD related pathology.
摘要
阿尔茨海默病（AD）发病机制的核心是正常的可溶性β-淀粉样蛋白（sAbeta）转变为寡聚体、纤维状的Aβ。这种构象转变过程会受到与其他能稳定疾病相关状态的蛋白质相互作用的影响；这些蛋白质被称为“病理性伴侣蛋白”。在许多AD模型中，阻断可溶性Aβ聚集的干预措施，包括β-折叠破坏剂，以及阻断与病理性伴侣蛋白相互作用的化合物，已被证明非常有效。当与早期病理检测相结合时，这些治疗策略有望成为预防AD相关病理的有效且相对无毒的方法。
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