Modeling neurodegenerative disorders in adult somatic cells: A critical review

Abstract

Development of new therapeutic targets for neurodegenerative disorders has been hampered by a reliance on post mortem tissue that is representative of end-stage disease, or on animal models that fail to provide faithful analogs. However, rapid advances in cellular genetic reprogramming, in particular the induction of somatic cells into stem cells, or directly into neurons, has led to intense interest in modeling of human neurodegeneration in vitro. Here, we critically review current methods and recent progress in cellular models of Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Several challenges are identified, including technical variability, lack of degenerative phenotypes, neurodevelopmental age and establishing ground truths for models of sporadic disease. Recommendations for evaluating neurodegenerative cellular models are proposed along with suggestions for future research.

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Compliance with ethics guidelines

An Truong, Emily Si, Thomas Duncan and Michael Valenzuela declare that they have no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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