LAUSR

Schizophrenia (SCZ) is a severe brain disorder, characterized by psychotic, negative and cognitive symptoms, affecting 1% of the population worldwide. The precise aetiology of SCZ is still unknown; however, SCZ has a high heritability, and is associated with genetic, environmental and social risk factors. Even though the genetic contribution is indisputable, the discrepancies between transcriptomics and proteomics in brain tissues are consistently challenging the field to decipher the disease pathology. Here we provide an overview of the state of the art of neuronal 2D and 3D model systems that can be combined with proteomics analyses to decipher specific brain pathology and detection of alternative entry points for drug development. © AlphaMed Press 2021 SIGNIFICANCE STATEMENT: This review article stresses the importance to implement complex 3D brain organoids (BOs) derived from human induced pluripotent stem cells. Those BOs should ideally have contributions from different brain regions as seen in so called assembloids where for example cortical and thalamic organoids are fused. Moreover it points out that protein and post translational modifications of proteins could be more relevant for disease development and progression. This is illustrated using the example of schizophrenia, a neurodevelopmental disease with highly diverse risk gene contribution. It is envisioned that such proposed approaches are highly relevant for complex neurological diseases.