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Although it is well established that such regulatory mechanisms become progressively impaired with aging, resulting in an accumulation of protein deposits, the specific nature of such impairment has remained incompletely characterized. Through a gene coexpression analysis, here we identify the endosomal\u2013lysosomal and ubiquitin\u2013proteasome systems, and more generally the protein trafficking and clearance mechanisms, as key components of the protein homeostasis system that maintains the metastable proteins in their functional states.<\/jats:p>","DOI":"10.1073\/pnas.1618417114","type":"journal-article","created":{"date-parts":[[2017,6,26]],"date-time":"2017-06-26T20:40:30Z","timestamp":1498509630000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":89,"title":["Protein homeostasis of a metastable subproteome associated with Alzheimer\u2019s disease"],"prefix":"10.1073","volume":"114","author":[{"given":"Rishika","family":"Kundra","sequence":"first","affiliation":[{"name":"Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United 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