The application of in vitro-derived human neurons in neurodegenerative disease modeling.
Alzheimer's disease
aging
direct conversion
iNs
iPSCs
induced neuron
induced pluripotent stem cells
neurodegenerative disease
stem cells
Journal
Journal of neuroscience research
ISSN: 1097-4547
Titre abrégé: J Neurosci Res
Pays: United States
ID NLM: 7600111
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
16
12
2019
revised:
19
02
2020
accepted:
27
02
2020
pubmed:
15
3
2020
medline:
3
11
2021
entrez:
15
3
2020
Statut:
ppublish
Résumé
The development of safe and effective treatments for age-associated neurodegenerative disorders is an on-going challenge faced by the scientific field. Key to the development of such therapies is the appropriate selection of modeling systems in which to investigate disease mechanisms and to test candidate interventions. There are unique challenges in the development of representative laboratory models of neurodegenerative diseases, including the complexity of the human brain, the cumulative and variable contributions of genetic and environmental factors over the course of a lifetime, inability to culture human primary neurons, and critical central nervous system differences between small animal models and humans. While traditional rodent models have advanced our understanding of neurodegenerative disease mechanisms, key divergences such as the species-specific genetic background can limit the application of animal models in many cases. Here we review in vitro human neuronal systems that employ stem cell and reprogramming technology and their application to a range of neurodegenerative diseases. Specifically, we compare human-induced pluripotent stem cell-derived neurons to directly converted, or transdifferentiated, induced neurons, as both model systems can take advantage of patient-derived human tissue to produce neurons in culture. We present recent technical developments using these two modeling systems, as well as current limitations to these systems, with the aim of advancing investigation of neuropathogenic mechanisms using these models.
Identifiants
pubmed: 32170790
doi: 10.1002/jnr.24615
pmc: PMC7487003
mid: NIHMS1569713
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
124-140Subventions
Organisme : NIA NIH HHS
ID : P30 AG066509
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005136
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG062148
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG052354
Pays : United States
Informations de copyright
© 2020 Wiley Periodicals, Inc.
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