title: Cycle on Wheels: Is APP Key to the AppBp1 Pathway?
abstract: Alzheimer's disease (AD) is the gradual loss of the cognitive function due to neuronal death. Currently no therapy is available to slow down, reverse or prevent the disease. Here we analyze the existing data in literature and hypothesize that the physiological function of the Amyloid Precursor Protein (APP) is activating the AppBp1 pathway and this function is gradually lost during the progression of AD pathogenesis. The AppBp1 pathway, also known as the neddylation pathway, activates the small ubiquitin-like protein nedd8, which covalently modifies and switches on Cullin ubiquitin ligases, which are essential in the turnover of cell cycle proteins. Here we discuss how APP may activate the AppBp1 pathway, which downregulates cell cycle markers and protects genome integrity. More investigation of this mechanism-driven hypothesis may provide insights into disease treatment and prevention strategies.
authors.affiliation: Department of Geriatrics, University of Arkansas for Medical Sciences, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, USA.
authors.forename: Rn
authors.initials: R
authors.lastname: Neve
authors.affiliation: Huffington Center on Aging, Baylor College of Medicine, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, USA.
authors.forename: Wts
authors.initials: W
authors.lastname: Griffin
authors.affiliation: Department of Pathology, University of Toledo Health Sciences Campus, USA.
authors.forename: Sw
authors.initials: S
authors.lastname: Barger
authors.forename: Re
authors.initials: R
authors.lastname: Mrak
keywords: APP; Alzheimer's disease; Cell cycle; Neddylation; Ubiquitination