Modeling motor neuron disease: the matter of time
Abstract
Stem cell technologies have created new opportunities to generate unlimited numbers of human neurons in the lab and study neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). Although some disease hallmarks have been reported in patient-derived stem cell models, it is proving more difficult to recapitulate the full phenotypic extent of these disorders. The problem with these stem cell models lies in the disparity between the advanced age of onset of neurodegenerative disorders and the embryonic nature of the in vitro derived cell types. In this review we discuss experimental methods of in vitro aging of neural cell types as a means to elicit late-onset symptoms in induced pluripotent stem cell (iPSC) models of neurodegenerative disease.
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iPSC neurons exhibit a fetal neuronal identity that might not be optimally suited to model all disease-relevant phenotypes.
“They are also known to exhibit a fetal neuronal identity that might not be optimally suited to model all disease-relevant phenotypes (Arbab et al., 2014; Luo et al., 2016; Patterson et al., 2012).”
From Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer’s patients (2021) · cites this paper as Arbab et al., 2014
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HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients
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“Recently, experimental manipulations to accelerate aging in iPSC-derived cells have been explored, for instance, by overexpressing progerin, a mutant form of lamin A observed in progeria syndrome, to force the detection of agerelated pathophysiology of neurodegenerative disease (Arbab et al., 2014; Cornacchia and Stud…”
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Disease modelling using human iPSCs
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Limitations and Challenges in Modeling Diseases Involving Spinal Motor Neuron Degeneration in Vitro
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IN VITRO MODEL SYSTEMS FOR INVESTIGATION OF MOTONEURON DEVELOPMENT AND DISEASE
Toma, J. S. (2016) · DalSpace (Dalhousie University)
Development of a Functional Testing Platform for the Sensory Segment of the Neuromuscular Reflex Arc
Colón, A. (2019) · Journal of International Crisis and Risk Communication Research
Modelling late-onset diseases with induced pluripotent stem cells: a matter of time management
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Modeling human neurodegeneration with iPSCs: opportunities, limitations, and the challenge of aging
Wang, S., Elia, L., Liu, W., & Finkbeiner, S. M. (2026) · Journal of Clinical Investigation · doi:10.1172/jci209602
- Authors
- Arbab, M., Baars, S., & Geijsen, N.
- Affiliations
- Utrecht University (NL)
- University Medical Center Utrecht (NL)
- Corresponding author
- Geijsen, Niels
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 37
- Issue
- 11
- Pages
- 642-652
- ISSN
- 0166-2236 (ISSN-L)
- OpenAlex
- W2101631778
- Cited by
- 33
- References
- 141
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 6 · 2015: 4
- FWCI
- 0.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Keywords
- motor neuron disease, amyotrophic lateral sclerosis, spinal muscular atrophy, induced pluripotent stem cells, in vitro aging, disease modeling, patient-derived neurons, neurodegeneration, late-onset symptoms
- MeSH terms
- Animals, Cell Differentiation, Disease Models, Animal, Humans, Motor Neurons, Stem Cells, Time Factors, Neurodegenerative Diseases
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