Rinaldi, F., Motti, D., Ferraiuolo, L. orcid.org/0000-0001-9118-5714 et al. (1 more author) (2017) High Content Analysis in Amyotrophic Lateral Sclerosis. Molecular and Cellular Neuroscience, 80. pp. 180-191. ISSN 1044-7431
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a devastating disease characterized by the progressive loss of motor neurons. Neurons, astrocytes, oligodendrocytes and microglial cells all undergo pathological modifications in the onset and progression of ALS. A number of genes involved in the etiopathology of the disease have been identified, but a complete understanding of the molecular mechanisms of ALS has yet to be determined. Currently, people affected by ALS have a life expectancy of only two to five years from diagnosis. The search for a treatment has been slow and mostly unsuccessful, leaving patients in desperate need of better therapies. Until recently, most pre-clinical studies utilized the available ALS animal models. In the past years, the development of new protocols for isolation of patient cells and differentiation into relevant cell types has provided new tools to model ALS, potentially more relevant to the disease itself as they directly come from patients. The use of stem cells is showing promise to facilitate ALS research by expanding our understanding of the disease and help to identify potential new therapeutic targets and therapies to help patients. Advancements in High Content Analysis (HCA) have the power to contribute to move ALS research forward by combining automated image acquisition along with digital image analysis. With modern HCA machines it is possible, in a period of just a few hours, to observe changes in morphology and survival of cells, under the stimulation of hundreds, if not thousands of drugs and compounds. In this article, we will summarize the major molecular and cellular hallmarks of ALS, describe the advancements provided by the in vitro models developed in the last few years, and review the studies that have applied HCA to the ALS field to date.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Elsevier. This is an author produced version of a paper subsequently published in Molecular and Cellular Neuroscience. Uploaded in accordance with the publisher's self-archiving policy. Article available under the terms of the CC-BY-NC-ND licence (https://creativecommons.org/licenses/by-nc-nd/4.0/) |
Keywords: | Amyotrophic lateral sclerosis; astrocytes; co-cultures; high content screening; motor neurons; neurodegeneration |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Neuroscience (Sheffield) |
Funding Information: | Funder Grant number THIERRY LATRAN FOUNDATION FTL AAP 2016 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 21 Dec 2016 13:03 |
Last Modified: | 29 Jan 2018 11:23 |
Published Version: | https://doi.org/10.1016/j.mcn.2016.12.001 |
Status: | Published |
Publisher: | Elsevier |
Refereed: | Yes |
Identification Number: | 10.1016/j.mcn.2016.12.001 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:109742 |