Department of Pathology and the Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
Prog Mol Biol Transl Sci. 2012;107:327-53. doi: 10.1016/B978-0-12-385883-2.00003-5.
The accumulation of misfolded proteins is a common feature of many neurodegenerative diseases. These observations suggest a potential link between these disorders and protein quality control, a collection of cellular pathways that sense damage to proteins and facilitate their turnover. Consistent with this idea, activation of quality control components, such as molecular chaperones, has been shown to be protective in multiple neurodegenerative disease models. In addition, key studies have suggested that quality control deteriorates with age, further supporting a relationship between these processes. In this chapter, we discuss the evidence linking neurodegeneration to quality control and present the emerging models. We also speculate on why proper quality control is so difficult for certain proteins.
蛋白质错误折叠的积累是许多神经退行性疾病的共同特征。这些观察结果表明，这些疾病与蛋白质质量控制之间可能存在联系，蛋白质质量控制是一组感知蛋白质损伤并促进其周转的细胞途径。与这一观点一致，已经证明激活质量控制成分，如分子伴侣，在多种神经退行性疾病模型中具有保护作用。此外，关键研究表明，质量控制随年龄的增长而恶化，进一步支持了这些过程之间的关系。在本章中，我们讨论了将神经退行性变与质量控制联系起来的证据，并提出了新兴模型。我们还推测为什么某些蛋白质的适当质量控制如此困难。
