Department of Cell and Developmental Biology, School of Medicine, University of North Carolina at Chapel Hill, 107 Mason Farm Road, Chapel Hill, NC 27514, United States.
Semin Cell Dev Biol. 2011 Jul;22(5):476-81. doi: 10.1016/j.semcdb.2011.03.011. Epub 2011 Mar 31.
Accumulation of amyloid-like aggregates is a hallmark of numerous neurodegenerative disorders such as Alzheimer's and polyglutamine disease. Yet, whether the amyloid inclusions found in these diseases are toxic or cytoprotective remains unclear. Various studies suggest that the toxic culprit in the amyloid folding pathway is actually a soluble oligomeric species which might interfere with normal cellular function by a multifactorial mechanism including aberrant protein-protein interactions. Molecular chaperones suppress toxicity of amyloidogenic proteins by inhibiting aggregation of non-native disease substrates and targeting them for refolding or degradation. Paradoxically, recent studies also suggest a protective action of chaperones in their promotion of the assembly of large, tightly packed, benign aggregates that sequester toxic protein species.
淀粉样样聚集物的积累是许多神经退行性疾病的标志，如阿尔茨海默病和多聚谷氨酰胺病。然而，这些疾病中发现的淀粉样包含物是有毒的还是细胞保护的仍然不清楚。各种研究表明，淀粉样折叠途径中的毒性罪魁祸首实际上是一种可溶性寡聚体，它可能通过多种机制，包括异常的蛋白-蛋白相互作用，干扰正常的细胞功能。分子伴侣通过抑制非天然疾病底物的聚集并将其靶向重折叠或降解来抑制淀粉样蛋白的毒性。矛盾的是，最近的研究也表明伴侣在促进大的、紧密堆积的良性聚集物组装方面具有保护作用，这些聚集物可以隔离有毒的蛋白质。
