Department of Genetics and Evolution, School of Biological Sciences, The University of Adelaide, Adelaide, SA 5005, Australia.
Hopwood Centre for Neurobiology, South Australian Health and Medical Research Institute, P.O. Box 11060, Adelaide, SA 5001, Australia.
Biomed Res Int. 2018 May 20;2018:5195416. doi: 10.1155/2018/5195416. eCollection 2018.
Autophagy is a conserved catabolic pathway that involves the engulfment of cytoplasmic components such as large protein aggregates and organelles that are delivered to the lysosome for degradation. This process is important in maintaining neuronal function and raises the possibility of a role for autophagy in neurodegenerative diseases. Alzheimer's disease (AD) is the most prevalent form of these diseases and is characterized by the accumulation of amyloid plaques in the brain which arise due to the misfolding and aggregation of toxic peptides, including amyloid beta (A). There is substantial evidence from both AD patients and animal models that autophagy is dysregulated in this disease. However, it remains to be determined whether this is protective or pathogenic as there is evidence that autophagy can act to promote the degradation as well as function in the generation of toxic A peptides. Understanding the molecular details of the extensive crosstalk that occurs between the autophagic and endolysosomal cellular pathways is essential for identifying the molecular details of amyloid toxicity. models that express the toxic proteins that aggregate in AD have been generated and have been shown to recapitulate hallmarks of the disease. Here we focus on what is known about the role of autophagy in amyloid toxicity in AD from mammalian models and how models can be used to further investigate AD pathogenesis.
自噬是一种保守的分解代谢途径，涉及细胞质成分（如大的蛋白质聚集体和细胞器）的吞噬，这些成分被递送到溶酶体进行降解。这个过程对于维持神经元功能很重要，并提出了自噬在神经退行性疾病中的作用的可能性。阿尔茨海默病（AD）是这些疾病中最常见的形式，其特征是大脑中淀粉样斑块的积累，这些斑块是由于有毒肽（包括淀粉样β（A））的错误折叠和聚集而产生的。有大量来自 AD 患者和动物模型的证据表明，自噬在这种疾病中失调。然而，目前还不清楚这是保护性的还是致病性的，因为有证据表明自噬可以促进有毒 A 肽的降解和功能。了解自噬和内溶酶体细胞途径之间广泛发生的分子细节对于确定淀粉样毒性的分子细节至关重要。已经产生了表达在 AD 中聚集的有毒蛋白的模型，并已显示出重现该疾病特征的能力。在这里，我们重点介绍从哺乳动物模型中了解到的自噬在 AD 中淀粉样毒性中的作用，以及如何使用这些模型来进一步研究 AD 的发病机制。
