High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases

ALDEWACHI, Hasan, AL-ZIDAN, Radhwan N., CONNER, Matthew T. and SALMAN, Mootaz M. (2021). High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases. Bioengineering, 8 (2).

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Open Access URL: https://www.mdpi.com/2306-5354/8/2/30#abstractc (Published version)
Link to published version:: https://doi.org/10.3390/bioengineering8020030
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    Abstract

    Neurodegenerative diseases (NDDs) are incurable and debilitating conditions that result in progressive degeneration and/or death of nerve cells in the central nervous system (CNS). Identification of viable therapeutic targets and new treatments for CNS disorders and in particular, for NDDs is a major challenge in the field of drug discovery. These difficulties can be attributed to the diversity of cells involved, extreme complexity of the neural circuits, the limited capacity for tissue regeneration, and our incomplete understanding of the underlying pathological processes. Drug discovery is a complex and multidisciplinary process. The screening attrition rate in current drug discovery protocols mean that only one viable drug may arise from millions of screened compounds resulting in the need to improve discovery technologies and protocols to address the multiple causes of attrition. This has identified the need to screen larger libraries where the use of efficient high-throughput screening (HTS) becomes key in the discovery process. HTS can investigate hundreds of thousands of compounds per day. However, if fewer compounds could be screened without compromising the probability of success, the cost and time would be largely reduced. To that end, recent advances in computer-aided design, in silico libraries, and molecular docking software combined with the upscaling of cell-based platforms have evolved to improve screening efficiency with higher predictability and clinical applicability. We review, here, the increasing role of HTS in contemporary drug discovery processes, in particular for NDDs, and evaluate the criteria underlying its successful application. We also discuss the requirement of HTS for novel NDD therapies and examine the major current challenges in validating new drug targets and developing new treatments for NDDs.

    Item Type: Article
    Additional Information: ** From MDPI via Jisc Publications Router ** Licence for this article: https://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 2306-5354 **History: published 23-02-2021; accepted 18-02-2021
    Uncontrolled Keywords: high-throughput screening, HTS, neurodegenerative diseases, drug discovery, dementia, brain diseases, CNS disorders, tauopathies, bioassays
    Identification Number: https://doi.org/10.3390/bioengineering8020030
    SWORD Depositor: Colin Knott
    Depositing User: Colin Knott
    Date Deposited: 26 Feb 2021 15:54
    Last Modified: 30 Mar 2021 12:15
    URI: http://shura.shu.ac.uk/id/eprint/28232

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