title: Mitotic signaling by beta-amyloid causes neuronal death.
abstract: Aggregates of beta-amyloid peptide (betaAP), the main constituent of amyloid plaques in Alzheimer's brain, kill neurons by a not yet defined mechanism, leading to apoptotic death. Here, we report that both full-length betaAP((1-40)) or ((1-42)) and its active fragment betaAP((25-35)) act as proliferative signals for differentiated cortical neurons, driving them into the cell cycle. The cycle followed some of the steps observed in proliferating cells, including induction of cyclin D1, phosphorylation of retinoblastoma, and induction of cyclin E and A, but did not progress beyond S phase. Inactivation of cyclin-dependent protein kinase-4 or -2 prevented both the entry into S phase and the development of apoptosis in betaAP((25-35))-treated neurons. We conclude that neurons must cross the G1/S transition before succumbing to betaAP signaling, and therefore multiple steps within this pathway may be targets for neuroprotective agents.-Copani, A., Condorelli, F., Caruso, A., Vancheri, C., Sala, A., Giuffrida Stella, A. M., Canonico, P. L., Nicoletti, F., Sortino, M. A. Mitotic signaling by beta-amyloid causes neuronal death.
authors.affiliation: Biochemistry and. Pharmacology, School of Medicine, University of Catania, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Copani
authors.forename: F
authors.initials: F
authors.lastname: Condorelli
authors.forename: A
authors.initials: A
authors.lastname: Caruso
authors.forename: C
authors.initials: C
authors.lastname: Vancheri
authors.forename: A
authors.initials: A
authors.lastname: Sala
authors.forename: A M
authors.initials: AM
authors.lastname: Giuffrida Stella
authors.forename: P L
authors.initials: PL
authors.lastname: Canonico
authors.forename: F
authors.initials: F
authors.lastname: Nicoletti
authors.forename: M A
authors.initials: MA
authors.lastname: Sortino
mesh_terms: D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D008938:Mitosis; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D018797:Cell Cycle Proteins