Toward Understanding Neurodegeneration Using Brain Organoids

Introduction: With the advancement of pluripotent stem cells (PSCs), several brain regions have been modelled through brain organoids that resemble their in vivo counterparts of the human brain in terms of cellular heterogeneity and gene expression. The models can be used for molecular pathogenesis studies of neurodegenerative diseases and can be combined with many recent technologies such as optogenetics, CRISPR/cas9, patch-clamp, or on-a-chip system to create more precise models of brain development and diseases. Moreover, personalised organoids derived from patient-specific induced pluripotent stem cells (iPSCs) can also be used to develop personalised treatment. This chapter introduces the principles of brain organoid formation and the potential uses of brain organoids for modelling neurodegenerative diseases, drug development, and personalised medicine. Methods: We performed a literature review in PubMed (https://www.pubmed.ncbi.nlm.nih.gov) using the keywords brain organoids; neural differentiation; neurodegeneration; personalised medicine. Conclusions: Personalised brain organoids, which can be derived by several approaches and coupled with genome editing such as CRISPR-Cas9, have proved to be powerful tools for in vitro studies of early human brain development and pathogenesis. Future treatment of incurable neurodegenerative disorders should ideally be tailored to individual patients to obtain optimal efficacy. To this end, using in vitro patient-specific models of neuroectodermal tissues will allow for such customised treatment personalised medicine.