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.
|Number of pages||7|
|Journal||Journal of Alzheimer's Disease|
|Publication status||Published - 2002|
ASJC Scopus subject areas
- Neuropsychology and Physiological Psychology