Modeling neurodegenerative diseases with cerebral organoids and other three-dimensional culture systems: focus on Alzhei
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Modeling neurodegenerative diseases with cerebral organoids and other three-dimensional culture systems: focus on Alzheimer’s disease Lalitha Venkataraman 1 & Summer R. Fair 2,3 & Craig A. McElroy 4 & Mark E. Hester 1,2,5 & Hongjun Fu 1 Accepted: 25 October 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Many neurodegenerative diseases (NDs) such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis and Huntington’s disease, are characterized by the progressive accumulation of abnormal proteinaceous assemblies in specific cell types and regions of the brain, leading to cellular dysfunction and brain damage. Although animal- and in vitro-based studies of NDs have provided the field with an extensive understanding of some of the mechanisms underlying these diseases, findings from these studies have not yielded substantial progress in identifying treatment options for patient populations. This necessitates the development of complementary model systems that are better suited to recapitulate human-specific features of ND pathogenesis. Three-dimensional (3D) culture systems, such as cerebral organoids generated from human induced pluripotent stem cells, hold significant potential to model NDs in a complex, tissue-like environment. In this review, we discuss the advantages of 3D culture systems and 3D modeling of NDs, especially AD and FTD. We also provide an overview of the challenges and limitations of the current 3D culture systems. Finally, we propose a few potential future directions in applying stateof-the-art technologies in 3D culture systems to understand the mechanisms of NDs and to accelerate drug discovery. Keywords Alzheimer’s disease . Neurodegenerative diseases . hiPSCs . 3D culture . cerebral organoids . tau pathology
Introduction This article belongs to the Topical Collection: Special issue on Neurogenesis and Neurodegeneration: Basic Research and Clinic Applications Guest Editor: Henning Ulrich * Mark E. Hester [email protected] * Hongjun Fu [email protected] 1
Department of Neuroscience, The Ohio State University Wexner Medical Center, 616 Biomedical Research Tower, 460 W. 12th Ave, Columbus, OH 43210, USA
2
The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, 575 Children’s Crossroad, Columbus, OH 43215, USA
3
College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA
4
College of Pharmacy, The Ohio State University, Columbus, OH, USA
5
Department of Pediatrics, The Ohio State University Wexner Medical Center, Columbus, OH, USA
Alzheimer’s disease (AD), Parkinson’s disease (PD), Frontotemporal dementia (FTD), Amyotrophic lateral sclerosis (ALS) and Huntington disease (HD) are devastating neurodegenerative diseases (NDs) that are prevalent worldwide, particularly in the elderly [1–3]. Although NDs are heterogeneous in their clinical manifestations and mechanisms of cellular vulnerabili
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