Neuronal apoptosis is accompanied by amyloid β-protein accumulation in the endoplasmic reticulum

Roberta Borghi, Luca Pellegrinib, Emanuela Lacanà, Alberto Diaspro, Maria Adelaide Pronzato, Antonella Vitali, Roberta Roncarati, Paola Strocchi, Damiano Zaccheo, Luciano D'Adamio, Massimo Tabaton

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

A series of evidences suggests that enhanced susceptibility to programmed cell death (PCD) is a major pathogenetic factor in Alzheimer's disease (AD). We investigated this issue, analyzing amyloid β-protein (Aβ) production in a model of neuronal PCD, induced by staurosporine in a murine neuroblastoma cell line. When PCD was induced, a 280-290% increase of respectively intracellular and secreted Aβ occurred, in spite of a 20% reduction of cellular metabolism and an unchanged AβPP expression. The increased intracellular Aβ reactivity largely colocalized with a marker of ER. Inhibition of caspases blocked the cleavage at the C-terminus of AβPP, but only partially rescued Aβ overproduction caused by staurosporine treatment. Our findings suggest that PCD fosters the physiological pathways of Aβ production characteristic of neuronal cells, and they confirm the theory that unbalance of PCD is a central event in AD pathogenesis. Moreover, our data indicate that still unidentified cellular mechanisms, other than caspases activation, are responsible of the specific alteration of AβPP processing during PCD.

Original languageEnglish (US)
Pages (from-to)31-37
Number of pages7
JournalJournal of Alzheimer's Disease
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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    Borghi, R., Pellegrinib, L., Lacanà, E., Diaspro, A., Pronzato, M. A., Vitali, A., Roncarati, R., Strocchi, P., Zaccheo, D., D'Adamio, L., & Tabaton, M. (2002). Neuronal apoptosis is accompanied by amyloid β-protein accumulation in the endoplasmic reticulum. Journal of Alzheimer's Disease, 4(1), 31-37. https://doi.org/10.3233/JAD-2002-4104