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

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 majo...

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Main Authors: Hasan Aldewachi, Radhwan N. Al-Zidan, Matthew T. Conner, Mootaz M. Salman
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Bioengineering
Subjects:
Online Access:https://www.mdpi.com/2306-5354/8/2/30
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author Hasan Aldewachi
Radhwan N. Al-Zidan
Matthew T. Conner
Mootaz M. Salman
author_facet Hasan Aldewachi
Radhwan N. Al-Zidan
Matthew T. Conner
Mootaz M. Salman
author_sort Hasan Aldewachi
collection DOAJ
description 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.
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spelling doaj.art-d50b761220e2440cb90bc5efa8d28fd42023-12-11T18:04:45ZengMDPI AGBioengineering2306-53542021-02-01823010.3390/bioengineering8020030High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative DiseasesHasan Aldewachi0Radhwan N. Al-Zidan1Matthew T. Conner2Mootaz M. Salman3Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield S1 1WB, UKCollege of Pharmacy, University of Mosul, Mosul 41002, IraqSchool of Sciences, Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton WV1 1LY, UKCollege of Pharmacy, University of Mosul, Mosul 41002, IraqNeurodegenerative 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.https://www.mdpi.com/2306-5354/8/2/30high-throughput screeningHTSneurodegenerative diseasesdrug discoverydementiabrain diseases
spellingShingle Hasan Aldewachi
Radhwan N. Al-Zidan
Matthew T. Conner
Mootaz M. Salman
High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases
Bioengineering
high-throughput screening
HTS
neurodegenerative diseases
drug discovery
dementia
brain diseases
title High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases
title_full High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases
title_fullStr High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases
title_full_unstemmed High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases
title_short High-Throughput Screening Platforms in the Discovery of Novel Drugs for Neurodegenerative Diseases
title_sort high throughput screening platforms in the discovery of novel drugs for neurodegenerative diseases
topic high-throughput screening
HTS
neurodegenerative diseases
drug discovery
dementia
brain diseases
url https://www.mdpi.com/2306-5354/8/2/30
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