In vitro cell culture is the essential method for the research of toxic or protective chemicals. However, isolated cells do not reflect the nature of the organism due to the lack of contact with other cells. In this case, organotypic cultures preserve the structure of the original tissue to better mimic in vivo conditions. Organotypic brain slice models represent a physiologically relevant three-dimensional model of the brain to support all cell types in the central nervous system (CNS). Derived from neurodegenerative disease related brain areas, our models allow a better understanding of neurodegenerative diseases and can be served as bridging technologies for the discovery of novel targets and therapeutic strategies.