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

Jokar, S ; Sharif University of Technology | 2019

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  1. Type of Document: Article
  2. DOI: 10.1007/s12551-019-00606-2
  3. Publisher: Springer , 2019
  4. Abstract:
  5. 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. © 2019, International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature
  6. Keywords:
  7. Amyloid-β fibrillation ; Computational methods ; Metal chelators ; Nanotechnology ; Neurodegenerative diseases ; Peptide inhibitors ; Advanced glycation end product receptor ; Amyloid beta protein ; Amyloid precursor protein ; Apolipoprotein E ; Carnosine ; Cell membrane protein ; Chelating agent ; Choline acetyltransferase ; Curcumin ; Diglycine ; Dipeptidyl carboxypeptidase ; Donepezil ; Edetic acid ; Epigallocatechin gallate ; Gold nanoparticle ; Imidazole ; Membrane metalloendopeptidase ; Penicillamine ; Pentetic acid ; Phenylalanine ; Phospholipid ; Phytoalexin ; Polyacrylic acid ; Povidone ; Presenilin 1 ; pullulan ; Reactive oxygen metabolite ; Rivastigmine ; Tacrine ; Triacylglycerol ; Allele ; Alzheimer disease ; Amyloid plaque ; Behavior disorder ; Blood brain barrier ; Cell migration ; Central nervous system ; Cerebrospinal fluid ; Chromosome 21 ; Cognitive defect ; Creutzfeldt Jakob disease ; Cytotoxicity ; Depolymerization ; Depression ; Down syndrome ; Drug design ; Enzyme stability ; Gene mutation ; Human ; Microglia ; Neurofibrillary tangle ; Neurotoxicity ; Nonhuman ; Parenchyma ; Parkinson disease ; Pathophysiology ; priority journal ; Protein aggregation ; Review ; Thrombocyte aggregation ; Transmission electron microscopy
  8. Source: Biophysical Reviews ; Volume 11, Issue 6 , 2019 , Pages 901-925 ; 18672450 (ISSN)
  9. URL: https://link.springer.com/article/10.1007/s12551-019-00606-2