PDF(Pubmed)
Abstract：
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.
摘要：
线粒体疾病是一组严重的病理，导致复杂的神经退行性疾病，在大多数情况下,没有治疗或治疗。这些细胞器是神经系统的神经发生和稳态的关键调节因子。因此,线粒体损伤或功能障碍可作为神经发育或神经退行性疾病的原因或结果而发生。随着神经发育障碍遗传知识的进步,已经确定了编码线粒体蛋白的基因与神经症状之间的关联，比如神经病,脑肌病,共济失调,癫痫发作,和发育迟缓，在其他人中。了解线粒体功能障碍如何改变这些过程对于研究罕见疾病至关重要。三维（3D）细胞培养，它们自组装形成由不同细胞类型组成的专门结构，代表了一种模拟器官发生和神经发育障碍的方法。特别是,脑类器官正在彻底改变基于线粒体的神经系统疾病的研究，因为它们是器官特异性的，并且是从患者的细胞产生的模型，从而克服了传统动物和细胞模型的一些局限性。在这次审查中,我们收集了在不同类型的脑类器官中概括的神经结构和功能，专注于作为线粒体疾病模型产生的那些。除了脑类器官产生的进步，技术,以及研究神经元结构和生理学的方法，在线粒体损伤和神经发育障碍的脑类器官中进行的药物筛选和药物重新定位研究也已被综述.本范围综述将总结有关研究脑类器官线粒体功能和动力学的局限性的证据。
