title: Cell cycle proteins in brain in mild cognitive impairment: insights into progression to Alzheimer disease.
abstract: Recent studies have demonstrated the re-emergence of cell cycle proteins in brain as patients progress from the early stages of mild cognitive impairment (MCI) into Alzheimer's disease (AD). Oxidative stress markers present in AD have also been shown to be present in MCI brain suggesting that these events occur in early stages of the disease. The levels of key cell cycle proteins, such as CDK2, CDK5, cyclin G1, and BRAC1 have all been found to be elevated in MCI brain compared to age-matched control. Further, peptidyl prolyl cis-trans isomerase (Pin1), a protein that plays an important role in regulating the activity of key proteins, such as CDK5, GSK3-β, and PP2A that are involved in both the phosphorylation state of Tau and in the cell cycle, has been found to be oxidatively modified and downregulated in both AD and MCI brain. Hyperphosphorylation of Tau then results in synapse loss and the characteristic Tau aggregation as neurofibrillary tangles, an AD hallmark. In this review, we summarized the role of cell cycle dysregulation in the progression of disease from MCI to AD. Based on the current literature, it is tempting to speculate that a combination of oxidative stress and cell cycle dysfunction conceivably leads to neurodegeneration.
authors.affiliation: Department of Chemistry, Center for Membrane Sciences, Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Jeriel T R
authors.initials: JT
authors.lastname: Keeney
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Swomley
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Harris
authors.forename: Ada
authors.initials: A
authors.lastname: Fiorini
authors.forename: Mihail I
authors.initials: MI
authors.lastname: Mitov
authors.forename: Marzia
authors.initials: M
authors.lastname: Perluigi
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Sultana
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000473:pathology* / Q000503:physiopathology*; D018450:Disease Progression; D006801:Humans
chemical_list: D018797:Cell Cycle Proteins
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