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Modeling neurodegenerative diseases with cerebral organoids and other
three-dimensional culture systems: focus on Alzheimer s disease
#MMPMID33180261
Venkataraman L
; Fair SR
; McElroy CA
; Hester ME
; Fu H
Stem Cell Rev Rep
2022[Feb]; 18
(2
): 696-717
PMID33180261
show ga
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 state-of-the-art technologies in 3D culture systems to understand the
mechanisms of NDs and to accelerate drug discovery. Graphical abstract.
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