Brain organoid as a model to study the role of mitochondria in neurodevelopmental disorders: achievements and weaknesses.

Autor:	Coronel R; Neural Regeneration Unit, Functional Unit for Research on Chronic Diseases (UFIEC), National Institute of Health Carlos III (ISCIII), Madrid, Spain.; Department of Systems Biology, Faculty of Medicine and Health Sciences, University of Alcalá (UAH), Alcalá de Henares, Spain., García-Moreno E; Andalusian Centre for Developmental Biology, CIBERER, National Institute of Health Carlos III (ISCIII), Pablo de Olavide University-CSIC-JA, Seville, Spain., Siendones E; Andalusian Centre for Developmental Biology, CIBERER, National Institute of Health Carlos III (ISCIII), Pablo de Olavide University-CSIC-JA, Seville, Spain., Barrero MJ; Models and Mechanisms Unit, Institute of Rare Diseases Research (IIER), Spanish National Institute of Health Carlos III (ISCIII), Madrid, Spain., Martínez-Delgado B; Molecular Genetics Unit, Institute of Rare Diseases Research (IIER), CIBER of Rare Diseases (CIBERER), Institute of Health Carlos III (ISCIII), Madrid, Spain., Santos-Ocaña C; Andalusian Centre for Developmental Biology, CIBERER, National Institute of Health Carlos III (ISCIII), Pablo de Olavide University-CSIC-JA, Seville, Spain., Liste I; Neural Regeneration Unit, Functional Unit for Research on Chronic Diseases (UFIEC), National Institute of Health Carlos III (ISCIII), Madrid, Spain., Cascajo-Almenara MV; Andalusian Centre for Developmental Biology, CIBERER, National Institute of Health Carlos III (ISCIII), Pablo de Olavide University-CSIC-JA, Seville, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular neuroscience [Front Cell Neurosci] 2024 Jun 24; Vol. 18, pp. 1403734. Date of Electronic Publication: 2024 Jun 24 (Print Publication: 2024).
DOI:	10.3389/fncel.2024.1403734
Abstrakt:	Mitochondrial diseases are a group of severe pathologies that cause complex neurodegenerative disorders for which, in most cases, no therapy or treatment is available. These organelles are critical regulators of both neurogenesis and homeostasis of the neurological system. Consequently, mitochondrial damage or dysfunction can occur as a cause or consequence of neurodevelopmental or neurodegenerative diseases. As genetic knowledge of neurodevelopmental disorders advances, associations have been identified between genes that encode mitochondrial proteins and neurological symptoms, such as neuropathy, encephalomyopathy, ataxia, seizures, and developmental delays, among others. Understanding how mitochondrial dysfunction can alter these processes is essential in researching rare diseases. Three-dimensional (3D) cell cultures, which self-assemble to form specialized structures composed of different cell types, represent an accessible manner to model organogenesis and neurodevelopmental disorders. In particular, brain organoids are revolutionizing the study of mitochondrial-based neurological diseases since they are organ-specific and model-generated from a patient's cell, thereby overcoming some of the limitations of traditional animal and cell models. In this review, we have collected which neurological structures and functions recapitulate in the different types of reported brain organoids, focusing on those generated as models of mitochondrial diseases. In addition to advancements in the generation of brain organoids, techniques, and approaches for studying neuronal structures and physiology, drug screening and drug repositioning studies performed in brain organoids with mitochondrial damage and neurodevelopmental disorders have also been reviewed. This scope review will summarize the evidence on limitations in studying the function and dynamics of mitochondria in brain organoids. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Coronel, García-Moreno, Siendones, Barrero, Martínez-Delgado, Santos-Ocaña and Cascajo-Almenara.)
Databáze:	MEDLINE
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