Myszczynska, M. and Ferraiuolo, L. orcid.org/0000-0001-9118-5714 (2016) New In Vitro Models to Study Amyotrophic Lateral Sclerosis. Brain Pathology, 26 (2). pp. 258-265. ISSN 1015-6305
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a complex multifactorial disorder, characterized by motor neuron loss with involvement of several other cell types, including astrocytes, oligodendrocytes and microglia. Studies in vivo and in in vitro models have highlighted that the contribution of non-neuronal cells to the disease is a primary event and ALS pathogenesis is driven by both cell-autonomous and non-cell autonomous mechanisms. The advancements in genetics and in vitro modeling of the past 10 years have dramatically changed the way we investigate the pathogenic mechanisms involved in ALS. The identification of mutations in transactive response DNA-binding protein gene (TARDBP), fused in sarcoma (FUS) and, more recently, a GGGGCC-hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9ORF72) and their link with familial ALS have provided new avenues of investigation and hypotheses on the pathophysiology of this devastating disease. In the same years, from 2007 to present, in vitro technologies to model neurological disorders have also undergone impressive developments. The advent of induced pluripotent stem cells (iPSCs) gave the field of ALS the opportunity to finally model in vitro not only familial, but also the larger part of ALS cases affected by sporadic disease. Since 2008, when the first human iPS-derived motor neurons from patients were cultured in a petri dish, several different techniques have been developed to produce iPSC lines through genetic reprogramming and multiple direct conversion methods have been optimised. In this review, we will give an overview of how human in vitro models have been used so far, what discoveries they have led to since 2007, and how the recent advances in technology combined with the genetic discoveries, have tremendously widened the horizon of ALS research.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 International Society of Neuropathology. This is an author produced version of a paper subsequently published in Brain Pathology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | astrocytes; cell models; iPSC; motor neurons |
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 MOTOR NEURONE DISEASE ASSOCIATION Ferraiuolo/Nov14/900-790 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 29 Sep 2016 11:17 |
Last Modified: | 12 Apr 2017 09:03 |
Published Version: | https://dx.doi.org/10.1111/bpa.12353 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1111/bpa.12353 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:97695 |