title: The role of ubiquitin-proteasome in the metabolism of amyloid precursor protein (APP): implications for novel therapeutic strategies for Alzheimer's disease.
abstract: The proteasome serves as a major protein quality control system inside the cell. Dysfunction of this system has been associated with Alzheimer's disease (AD) pathogenesis. Amyloid β accumulation is considered as the central molecular event in the development of AD. This accumulation can result from dysregulated proteolysis of its precursor, APP. Here, we will review the evidence that links proteasome dysfunction to altered APP metabolism, and summarize recent progress in identifying the regulators of APP ubiquitination. Pinpointing UPS components that are APP-specific could lead new pharmaceutical strategies to combat AD.
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA 19104, USA and Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors.forename: Haizhi
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA 19104, USA and Department of Neurobiology and Anatomy and Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
authors.forename: Aleister J
authors.initials: AJ
authors.lastname: Saunders
mesh_terms: D000544:Alzheimer Disease / Q000628:therapy*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D016564:Amyloid beta-Protein Precursor; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex