期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：28
页码：E5703-E5711
DOI：10.1073/pnas.1618417114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Alzheimer’s disease is the most common cause of dementia. A hallmark of this disease is the presence of aberrant deposits containing by the Aβ peptide (amyloid plaques) and the tau protein (neurofibrillary tangles) in the brains of affected individuals. Increasing evidence suggests that the formation of these deposits is closely associated with the age-related dysregulation of a large set of highly expressed and aggregation-prone proteins, which make up a metastable subproteome. To understand in more detail the origins of such dysregulation, we identify specific components of the protein homeostasis system associated with these metastable proteins by using a gene coexpression analysis. Our results reveal the particular importance of the protein trafficking and clearance mechanisms, including specific branches of the endosomal–lysosomal and ubiquitin–proteasome systems, in maintaining the homeostasis of the metastable subproteome associated with Alzheimer’s disease.
关键词：Alzheimer’s disease ; protein aggregation ; protein homeostasis ; supersaturation
