For example, microcephaly is a neurodevelopmental disorder in which brain size is markedly reduced. Nevertheless, considerable questions have emerged regarding the translatability of such animal-based research to human disease treatment since there are many differences in physiology, genetics and developmental patterns between human and animal brains ( 143, 144, 173, 237, 273, 416, 494). Since there are many inherent barriers to conducting research directly on human subjects and primary brain samples, animal models have played a major role in studying neurological disorder mechanisms for decades and have been at the forefront of evaluating novel therapeutic approaches ( 39, 41, 71, 225, 234, 242, 247, 347, 354, 414). Further research into the mechanistic causes of neurological disorders is essential for the development of new therapeutic approaches for disorders like AD. In its 2018 Annual Report ( 473), the Alzheimer’s Association estimated 5.7 million Americans are living with AD. For instance, Alzheimer’s Disease (AD) is one such prominent disease taking a major toll on the aging population and places a huge burden on the healthcare system. ![]() Many neurological disorders are chronic and incurable conditions with debilitating effects that may continue for years or even decades post-diagnosis. The causes and risk factors behind these diseases, including a combination of environmental and/or genetic factors, are complex and not well understood. ![]() Neurological disorders, such as neurodegenerative, neurodevelopmental, and psychiatric disorders, have emerged as a predominant healthcare concern in recent years, due to their severe consequences on quality of life and prevalence throughout the world. This review also covers the current status of applications of 2D, 3D and BBB models in drug screening, precision medicine, and modeling a wide range of neurological diseases (e.g., neurodegenerative diseases, neurodevelopmental disorders, brain injury, and neuropsychiatric disorders). In this review, we describe recent progress in the generation of 2D, 3D and BBB models from iPSCs and further discuss their limitations, advantages, and future ventures. As iPSCs can be generated from diverse patient populations, researchers have effectively applied 2D, 3D and BBB models to recapitulate genetically complex neurological disorders and reveal novel insights into molecular and genetic mechanisms of neurological disorders. ![]() These 3D organoids have gained widespread attention as in vitro tools to recapitulate complex features of the brain, and 3) Complex interactions between iPSC-derived brain cell types can recapitulate physiological and pathological conditions of blood-brain barrier (BBB). Mounting evidence shows: 1) various brain cells can be generated from iPSCs in 2-dimensional (2D) monolayer cultures 2) further advances in 3D culture systems have led to the differentiation of iPSCs into organoids with multiple brain cell types and specific brain regions. Induced pluripotent stem cells (iPSCs) are invaluable tools for neurological disease modeling, as they have unlimited self-renewal and differentiation capacity. Understanding the underlying mechanisms of these diseases and the interactions between different brain cell types is essential for the development of new therapeutics. Neurological disorders have emerged as a predominant healthcare concern in recent years due to their severe consequences on quality of life and prevalence throughout the world.
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