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Recent advances in the design and applications of amyloid-β peptide aggregation inhibitors for Alzheimer’s disease therapy

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Abstract

Alzheimer’s disease (AD) is an irreversible neurological disorder that progresses gradually and can cause severe cognitive and behavioral impairments. This disease is currently considered a social and economic incurable issue due to its complicated and multifactorial characteristics. Despite decades of extensive research, we still lack definitive AD diagnostic and effective therapeutic tools. Consequently, one of the most challenging subjects in modern medicine is the need for the development of new strategies for the treatment of AD. A large body of evidence indicates that amyloid-β (Aβ) peptide fibrillation plays a key role in the onset and progression of AD. Recent studies have reported that amyloid hypothesis–based treatments can be developed as a new approach to overcome the limitations and challenges associated with conventional AD therapeutics. In this review, we will provide a comprehensive view of the challenges in AD therapy and pathophysiology. We also discuss currently known compounds that can inhibit amyloid-β (Aβ) aggregation and their potential role in advancing current AD treatments. We have specifically focused on Aβ aggregation inhibitors including metal chelators, nanostructures, organic molecules, peptides (or peptide mimics), and antibodies. To date, these molecules have been the subject of numerous in vitro and in vivo assays as well as molecular dynamics simulations to explore their mechanism of action and the fundamental structural groups involved in Aβ aggregation. Ultimately, the aim of these studies (and current review) is to achieve a rational design for effective therapeutic agents for AD treatment and diagnostics.

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Acknowledgments

We would like to thank the Editorial Board Members of the Biophysical Reviews journal for their help in improving the clarity of expression of our manuscript.

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Authors and Affiliations

  1. Department of Nuclear Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. BOX: 14155-6559, Tehran, Iran

    Safura Jokar & Hossein Behnammanesh

  2. Department of Pharmaceutical Biomaterials , Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. BOX: 14155-6559, Tehran, Iran

    Saeedeh Khazaei

  3. Department of Mechanical Engineering, Sharif University of Technology, P.O. Box: 11365-11155, Tehran, Iran

    Amir Shamloo

  4. Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), P.O. Box: 14155-1339, Tehran, Iran

    Mostafa Erfani

  5. Research Center for Nuclear Medicine, Tehran University of Medical Sciences, P.O. BOX: 14155-6559, Tehran, Iran

    Davood Beiki

  6. Department of Mechanical and Aerospace Engineering, Shiraz University of Technology, P.O. Box: 71555-313, Shiraz, Iran

    Omid Bavi

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  1. Safura Jokar
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  2. Saeedeh Khazaei
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  3. Hossein Behnammanesh
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  7. Omid Bavi
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Correspondence to Omid Bavi.

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Jokar, S., Khazaei, S., Behnammanesh, H. et al. Recent advances in the design and applications of amyloid-β peptide aggregation inhibitors for Alzheimer’s disease therapy. Biophys Rev 11, 901–925 (2019). https://doi.org/10.1007/s12551-019-00606-2

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