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Cited by 32Alzheimer's disease research and treatmentsCell death mechanisms and regulationNeuroinflammation and Neurodegeneration Mechanisms

Cell death assays for neurodegenerative disease drug discovery

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Linsley, Jeremy W., Reisine, Terry, Finkbeiner, Steven·2019·Expert Opinion on Drug Discovery
DOI 10.1080/17460441.2019.1623784PMC PMC6663635
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Abstract

Introduction: Neurodegenerative diseases affect millions of people worldwide. Neurodegeneration is gradual over time, characterized by neuronal death that causes deterioration of cognitive or motor functions, ultimately leading to the patient’s death. Currently, there are no treatments that effectively slow the progression of any neurodegenerative disease, but improved microscopy assays and models for neurodegeneration could lead the way to the discovery of disease-modifying therapeutics.Areas covered: Herein, the authors describe cell-based assays used to discover drugs with the potential to slow neurodegeneration, and their associated disease models. They focus on microscopy technologies that can be adapted to a high-throughput screening format that both detect cell death and monitor early signs of neurodegeneration and functional changes to identify drugs that the block early stages of neurodegeneration.Expert opinion: Many different phenotypes have been used in screens for the development of therapeutics towards neurodegenerative disease. The context of each phenotype in relation to neurodegeneration must be established to identify therapeutics likely to successfully target and treat disease. The use of improved models of neurodegeneration, statistical analyses, computational models, and improved markers of neuronal death will help in this pursuit and lead to better screening methods to identify therapeutic compounds against neurodegenerative disease.

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  • TUNEL staining detects DNA breaks formed during cellular apoptosis and is a widely applied histological method used to measure neurodegeneration.

    “TUNEL staining, which detects DNA breaks formed during cellular apoptosis, is a widely applied histological method used to measure neurodegeneration (Linsley et al. 2019).”

    From Perineuronal net deglycosylation associates with tauopathy‐induced gliosis and neurodegeneration (2024) · cites this paper as Linsley et al. 2019

    The “High throughput cell death screening assays” section says TUNEL monitors DNA fragmentation preceding death and was used to read out neuronal death in a β-amyloid toxicity screen. It does not describe TUNEL as a widely applied histological measure of neurodegeneration or say that the DNA breaks it detects are specific to apoptosis; the “Apoptosis” section cautions that neurodegenerative cell death is not exclusively apoptotic. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Linsley, J. W., Reisine, T., & Finkbeiner, S.
Affiliations
  • Gladstone Institutes (US)
  • Independent scientific consultant, Santa Cruz, CA, USA
Corresponding author
Finkbeiner, Steven
ORCID
Venue
Expert Opinion on Drug Discovery
Publisher
Informa UK Limited
Published
2019-06-10
Volume
14
Issue
9
Pages
901-913
ISSN
  • 1746-0441 (ISSN-L)
  • 1746-045X
DOI
10.1080/17460441.2019.1623784
PMC
PMC6663635
OpenAlex
W2950163825
Cited by
32
References
6
Citations by year
2026: 1 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 9 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1
FWCI
0.41
Type
journal article
Language
en
Open access
Locations
  • Expert Opinion on Drug Discovery (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
National Institutes of Health (1P01AG054407, 1R37NS101996, 1RF1AG056151, 1RF1AG058476, 5U54NS091046)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
neurodegenerative diseases, neuronal cell death, cell death assays, high-throughput screening, disease-modifying therapy, neurodegeneration model, drug discovery
MeSH terms
Drug Development, Animals, Humans, Models, Biological, Phenotype, Cell Death, Neurodegenerative Diseases, Drug Discovery, High-Throughput Screening Assays

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