Emerging Brain‐Pathophysiology‐Mimetic Platforms for Studying Neurodegenerative Diseases: Brain Organoids and Brains‐on‐a‐Chip

Abstract Neurodegenerative diseases are a group of disorders characterized by progressive degeneration of the structural and functional integrity of the central and peripheral nervous systems. Millions of people suffer from degenerative brain diseases worldwide, and the mortality continues to increase every year, causing a growing demand for knowledge of the underlying mechanisms and development of therapeutic targets. Conventional 2D‐based cell culture platforms and animal models cannot fully recapitulate the pathophysiology, and this has limited the capability for estimating drug efficacy. Recently, engineered platforms, including brain organoids and brain‐on‐a‐chip, have emerged. They mimic the physiology of brain tissue and reflect the fundamental pathophysiological signatures of neurodegenerative diseases, such as the accumulation of neurotoxic proteins, structural abnormalities, and functional loss. In this paper, recent advances in brain‐mimetic platforms and their potential for modeling features of neurodegenerative diseases in vitro are reviewed. The development of a physiologically relevant model should help overcome unresolved neurodegenerative diseases.