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

• Published in: Biophysical reviews Vol. 11; no. 6; pp. 901 - 925
• Main Authors: Jokar, Safura, Khazaei, Saeedeh, Behnammanesh, Hossein, Shamloo, Amir, Erfani, Mostafa, Beiki, Davood, Bavi, Omid
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2019; Springer Nature B.V
• Subjects: Agglomeration; Alzheimer's disease; Antibodies; Biochemistry; Biological and Medical Physics; Biological Techniques; Biomedical and Life Sciences; Biophysics; Cell Biology; Chelating agents; Chemical compounds; Cognitive ability; Diagnostic software; Diagnostic systems; Drug development; Fibrillation; Inhibitors; Life Sciences; Membrane Biology; Molecular dynamics; Nanotechnology; Neurological diseases; Organic chemistry; Pathophysiology; Peptides; Pharmacology; Review; Therapy; β-Amyloid; Computational methods; Peptide inhibitors; Neurodegenerative diseases; Amyloid-β fibrillation; Metal chelators; Nanotechnology
• ISSN: 1867-2450; 1867-2469
• DOI: 10.1007/s12551-019-00606-2

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.