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

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Abstract

Accumulation of beta-amyloid (Aβ) peptides in senile plaques is one of the pathological hallmarks in Alzheimer's disease (AD), which can trigger apoptosis. We have previously demonstrated that Aβ triggered calcium release from the ER. Depletion of ER Ca2+ 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 Aβ on UPR. We have shown previously that activation of PKR in Aβ-triggered apoptosis. Since UPR can trigger PKR, our study aims to elucidate whether extracellular accumulation of Aβ peptides induce UPR in cultured neurons. Our results showed that Aβ 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 Aβ peptides induce apoptosis via a mechanism independent of UPR.

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Authors and Affiliations

  1. Laboratory of Neurodegenerative Diseases, Department of Anatomy, Research Centre of Heart, Brain, Hormone and Healthy Aging, Faculty of Medicine, The University of Hong Kong, Hong Kong SAR

    Man-Shan Yu, Ka-Chun Suen, Nga-Sze Kwok, Kwok-Fai So & Raymond Chuen-Chung Chang

  2. Department of Neurology, University of Poitiers and Poitiers University Hospital, France

    Jacques Hugon

  3. Department of Anatomy, Faculty of Medicine, The University of Hong Kong, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong

    Raymond Chuen-Chung Chang

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  1. Man-Shan Yu
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  2. Ka-Chun Suen
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  3. Nga-Sze Kwok
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  4. Kwok-Fai So
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Correspondence to Raymond Chuen-Chung Chang.

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Yu, MS., Suen, KC., Kwok, NS. et al. Beta-amyloid peptides induces neuronal apoptosis via a mechanism independent of unfolded protein responses. Apoptosis 11, 687–700 (2006). https://doi.org/10.1007/s10495-006-5540-1

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