title: Alzheimer's disease meets the ubiquitin-proteasome system.
abstract: Ubiquitin-positive deposits are histopathologically found in patients with Alzheimer's disease (AD). It is not understood why ubiquitin is accumulated in intra- and extra-cellular deposits or how it is involved in AD pathogenesis. Interestingly, recent evidence, including studies of E2-25K/Hip-2, has elucidated the molecular mechanism of the ubiquitin-proteasome system (UPS) malfunction in AD. The neurotoxicity and proteasome inhibition by Abeta, a main cause of AD pathogenesis, are mediated by increased E2-25K/Hip-2 in the brains of patients with AD. Furthermore, E2-25K/Hip-2 is required for the neurotoxicity that is mediated by a ubiquitin B mutant (UBB+1), which is a potent inhibitor of proteasomes that is found in patients with AD. Intensive research is required to identify the components of the UPS that are involved in AD pathogenesis.
authors.affiliation: Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.
authors.forename: Sungmin
authors.initials: S
authors.lastname: Song
authors.forename: Yong-Keun
authors.initials: YK
authors.lastname: Jung
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000235:genetics; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D061988:Proteasome Inhibitors; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000502:physiology*; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: D061988:Proteasome Inhibitors; D014452:Ubiquitins; C100879:UBE2K protein, human; D044763:Ubiquitin-Conjugating Enzymes; D046988:Proteasome Endopeptidase Complex