Mitotic signaling by β-amyloid causes neuronal death

A. Copani, F. Condorelli, A. Caruso, C. Vancheri, A. Sala, A. M G Stella, P. L. Canonico, F. Nicoletti, M. A. Sortino

Research output: Contribution to journalArticlepeer-review


Aggregates of β-amyloid peptide (βAP), 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 βAP((1- 40)) or ((1-42)) and its active fragment βAP((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 βAP((2535))-treated neurons. We conclude that neurons must cross the G1/S transition before succumbing to βAP 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 β-amyloid causes neuronal death.

Original languageEnglish
Pages (from-to)2225-2234
Number of pages10
JournalFASEB Journal
Issue number15
Publication statusPublished - 1999


  • Alzheimer's disease
  • Cell cycle
  • Neuronal apoptosis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology


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