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Title

Ca2+/calmodulin-dependent modulation of cell cycle elements pRb and p27kip1 involved in the enhanced proliferation of lymphoblasts from patients with Alzheimer dementia

AuthorsDe las Cuevas, Natividad; Urcelay, Elena; García-Hermida, Ofelia; Saíz-Diaz, Rosa A.; Bermejo-Pareja, Félix; Sánchez Ayuso, Matilde ; Martín-Requero, Ángeles
Issue Date2003
PublisherElsevier
CitationNeurobiology of Disease 13(3):254-263(2003)
AbstractFailure of cell cycle regulation in neurons might be critically involved in the process of neurodegeneration in Alzheimer's disease (AD). We present here evidence to support the hypothesis that cell cycle alterations occur in cells other than neurons in AD sufferers. Lymphocytes from AD patients immortalized with Epstein-Barr virus showed an enhanced rate of proliferation and increased phosphorylation of the retinoblastoma protein (pRb) and other members of the family of pocket proteins compared with cell lines derived from normal age-matched controls. The calmodulin antagonist calmidazolium, as well as W-7 and W-13, abrogated the enhanced activity of AD cells without altering the normal basal rate of proliferation. The effect of calmidazolium was accompanied by partially dephosphorylation of pRb. No changes were found in the expression levels of the G1 cyclin/Cdks complexes. However, lymphoblasts derived from AD patients showed reduced levels of the Cdk inhibitor p27kip1, which were restored after anti-calmodulin treatment of the cultures. These observations suggest that in AD cells the enhanced rates of cell proliferation and phosphorylation of pRb and the intracellular content of p27kip1 may be interrelated events controlled by a mechanism dependent on the Ca2+/calmodulin signaling pathway. The distinct functional features of lymphoblastoid cells from AD patients offer an invaluable, noninvasive tool to investigate the etiopathogenesis, and eventually, for the early diagnosis and prognosis of this devastating disease. © 2003 Elsevier Science (USA). All rights reserved.
URIhttp://hdl.handle.net/10261/72389
DOI10.1016/S0969-9961(03)00040-8
Identifiersdoi: 10.1016/S0969-9961(03)00040-8
issn: 0969-9961
e-issn: 1095-953X
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