title: Cell cycle re-entry mediated neurodegeneration and its treatment role in the pathogenesis of Alzheimer's disease.
abstract: As one of the earliest pathologic changes, the aberrant re-expression of many cell cycle-related proteins and inappropriate cell cycle control in specific vulnerable neuronal populations in Alzheimer's disease (AD) is emerging as an important component in the pathogenesis leading to AD and other neurodegenerative diseases. These events are clearly representative of a true cell cycle, rather than epiphenomena of other processes since, in AD and other neurodegenerative diseases, there is a true mitotic alteration that leads to DNA replication. While the exact role of cell cycle re-entry is unclear, recent studies using cell culture and animal models strongly support the notion that the dysregulation of cell cycle in neurons leads to the development of AD-related pathology such as hyperphosphorylation of tau and amyloid-beta deposition and ultimately causes neuronal cell death. Importantly, cell cycle re-entry is also evident in mutant amyloid-beta precursor protein and tau transgenic mice and, as in human disease, occurs prior to the development of the pathological hallmarks, neurofibrillary tangles and amyloid-beta plaques. Therefore, the study of aberrant cell cycle regulation in model systems, both cellular and animal, may provide extremely important insights into the pathogenesis of AD and also serve as a means to test novel therapeutic approaches.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, OH, USA. hyoung-gon.lee@case.edu
authors.forename: Hyoung-Gon
authors.initials: HG
authors.lastname: Lee
authors.forename: Gemma
authors.initials: G
authors.lastname: Casadesus
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
authors.forename: Rudy J
authors.initials: RJ
authors.lastname: Castellani
authors.forename: Andrew
authors.initials: A
authors.lastname: McShea
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Robert B
authors.initials: RB
authors.lastname: Petersen
authors.forename: Vladan
authors.initials: V
authors.lastname: Bajic
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D006801:Humans; D009410:Nerve Degeneration / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D053763:Presenilins / Q000378:metabolism / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D053763:Presenilins; D016875:tau Proteins