The Effect Of Overexpressing Mutant Amyloid-(A)Over-Cap Protein Precursor And Its A(A)Over-Cap Fragments In Sh-Sy5y Cells

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Its histopathologic hallmarks include progressive loss of neurons, synaptic depredation, the presence of intracellular neurofibrillary tangles and extracellular senile plaques, which composed mainly of amyloid â-peptide (Aâ), a 40–42-amino acid peptide derived from proteolytic cleavage of amyloid-â protein precursor (AâPP). Most of the familial Alzheimer's disease has been correlated with inherited mutations in presenilins (PS1 and PS2) and their substrate, APP. The etiology of AD is unknown. To investigate the mechanism of toxicity induced by Aâ, we established several stable SH-SY5Y cell lines which over expressed mutant amyloid-â protein precursor and its fragments. With this cell model, we observed an increase in superoxide radical anions and hydrogen peroxide generation in cells overexpressing mutant amyloid-â protein precursor and its fragments. In addition, both cytosolic Ca (II) level and caspase-3 activity were also elevated. These results will be discussed in light of the notion that the dysregulation of Ca (II) homeostasis may play the key factor to induce the apoptosis in the cell lines in which reactive oxygen species was elevated due to Aâ and Aâ mutant overexpression.