title: Cellular proteostasis: degradation of misfolded proteins by lysosomes.
abstract: Proteostasis refers to the regulation of the cellular concentration, folding, interactions and localization of each of the proteins that comprise the proteome. One essential element of proteostasis is the disposal of misfolded proteins by the cellular pathways of protein degradation. Lysosomes are an important site for the degradation of misfolded proteins, which are trafficked to this organelle by the pathways of macroautophagy, chaperone-mediated autophagy and endocytosis. Conversely, amyloid diseases represent a failure in proteostasis, in which proteins misfold, forming amyloid deposits that are not degraded effectively by cells. Amyloid may then exacerbate this failure by disrupting autophagy and lysosomal proteolysis. However, targeting the pathways that regulate autophagy and the biogenesis of lysosomes may present approaches that can rescue cells from the deleterious effects of amyloidogenic proteins.
authors.affiliation: School of Molecular and Cellular Biology and the Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, U.K.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Jackson
authors.affiliation: School of Molecular and Cellular Biology and the Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, U.K. e.w.hewitt@leeds.ac.uk.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Hewitt
mesh_terms: D000682:Amyloid / Q000378:metabolism; D000818:Animals; D002477:Cells / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D059748:Proteolysis
chemical_list: D000682:Amyloid; D011506:Proteins
keywords: Parkinson's disease; TFEB; amyloid; autophagy; chaperone-mediated autophagy; immunoglobulin light chain; lysosome; mTOR; macroautophagy; protein aggregation; protein misfolding; proteostasis; rapamycin; α-synuclein; β2-microglobulin