Beta-amyloid peptides induces neuronal apoptosis via a mechanism independent of unfolded protein responses

Accumulation of beta-amyloid (A beta) peptides in senile plaques is one of the pathological hallmarks in Alzheimer's disease (AD), which can trigger apoptosis. We have previously demonstrated that A beta triggered calcium release from the ER. Depletion of ER Ca2+ stop ions has been reported leading to unfolded protein responses (UPR). While hypothesis has been made about UPR and neurodegeneration in AD, little is known about the effects of extracellular accumulation of A beta on UPR. We have shown previously that activation of PKR in A beta-triggered apoptosis. Since UPR can trigger PKR, our study aims to elucidate whether extracellular accumulation of A beta peptides induce UPR in cultured neurons. Our results showed that A beta could not trigger UPR signalings including phosphorylation of PERK, alternative cleavage of xbp-1 mRNA and induction of transcription of xbp-1 and Gadd153. Taken together, our results suggest that extracellular accumulation of A beta peptides induce apoptosis via a mechanism independent of UPR.