title: Emerging role of Alzheimer's disease-associated ubiquilin-1 in protein aggregation.
abstract: Abnormal protein aggregation and intracellular or extracellular accumulation of misfolded and aggregated proteins are key events in the pathogenesis of different neurodegenerative diseases. Furthermore, endoplasmic reticulum stress and impairment of the ubiquitin-proteasome system probably contribute to neurodegeneration in these diseases. A characteristic feature of AD (Alzheimer's disease) is the abnormal accumulation of Abeta (amyloid beta-peptide) in the brain. Evidence shows that the AD-associated PS (presenilin) also forms aggregates under certain conditions and that another AD-associated protein, ubiquilin-1, controls protein aggregation and deposition of aggregated proteins. Here, we review the current knowledge of ubiquilin-1 and PS in protein aggregation and related events that potentially influence neurodegeneration.
authors.affiliation: Department of Neurology, University of Kuopio, and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Annakaisa
authors.initials: A
authors.lastname: Haapasalo
authors.forename: Jayashree
authors.initials: J
authors.lastname: Viswanathan
authors.forename: Lars
authors.initials: L
authors.lastname: Bertram
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: Mikko
authors.initials: M
authors.lastname: Hiltunen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D018384:Oxidative Stress; D053763:Presenilins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016229:Amyloid beta-Peptides; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D053763:Presenilins; C107792:UBQLN1 protein, human; D046988:Proteasome Endopeptidase Complex