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Modulation of Alzheimer's amyloid β peptide oligomerization and toxicity by extracellular Hsp70

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Cell Stress and Chaperones Aims and scope

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder leading to dementia caused by advanced neuronal dysfunction and death. The most significant symptoms of AD are observed at late stages of the disease when interventions are most likely too late to ameliorate the condition. Currently, the predominant theory for AD is the “amyloid hypothesis,” which states that abnormally increased levels of amyloid β (Aβ) peptides result in the production of a variety of aggregates that are neurotoxic. The specific mechanisms for Aβ peptide-induced cytotoxicity have not yet been completely elucidated. However, since the majority of Aβ is released into the extracellular milieu, it is reasonable to assume that toxicity begins outside the cells and makes its way inside where it disrupts the basic cellular process resulting in cell death. There is increasing evidence that hsp, particularly Hsp70, are exported into the extracellular milieu by an active export mechanism independent of cell death. Therefore, both Aβ peptides and Hsp70 may coexist in a common environment during pathological conditions. We observed that Hsp70 affected the Aβ assembling process in vitro preventing oligomer formation. Moreover, the presence of Hsp70 reduced the Aβ peptide-induced toxicity of cultured neurons (N2A cells). These results suggest a potential mechanism for the reduction of the detrimental effects of Aβ peptides in AD.

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Acknowledgements

We would like to thank Barbara Rho for her excellent editing of the manuscript.

Funding

This work was supported by National Institutes of Health (NIH) Grant R01 GM11447 and UC San Diego Academic Senate grant.

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Authors and Affiliations

  1. Division of Trauma, Critical Care, Burns and Acute Care Surgery, Department of Surgery and Department of Neurosciences, School of Medicine, University of California San Diego, 9500 Gilman Drive, #0739, La Jolla, 92093-0739, CA, USA

    Isabel Rivera, Ricardo Capone, David M. Cauvi & Antonio De Maio

  2. Initiative for Maximizing Student Development (IMSD) Program, University of California San Diego, La Jolla, CA, USA

    Isabel Rivera

  3. Department of Anatomy, Physiology and Genetics, Uniformed Services University School of Medicine, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA

    Nelson Arispe

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  1. Isabel Rivera
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Correspondence to Antonio De Maio.

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Rivera, I., Capone, R., Cauvi, D.M. et al. Modulation of Alzheimer's amyloid β peptide oligomerization and toxicity by extracellular Hsp70. Cell Stress and Chaperones 23, 269–279 (2018). https://doi.org/10.1007/s12192-017-0839-0

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