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The effect of overexpressing mutant amyloid‐â protein precursor and its Aâ fragments in SH‐SY5Y cells
Author(s) -
Zhao Hongtao,
Li Tianwei,
Yu Shiqin,
Chock Boon
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.309
Subject(s) - senile plaques , presenilin , amyloid precursor protein , mutant , chemistry , p3 peptide , alzheimer's disease , programmed cell death , intracellular , amyloid (mycology) , apoptosis , microbiology and biotechnology , caspase , extracellular , biochemistry , biology , medicine , disease , inorganic chemistry , gene
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.