High-throughput platforms for the screening of new therapeutic targets for neurodegenerative diseases

• Published in: Drug discovery today 2016-09, Vol.21 (9), p.1355-1366
• Main Authors: Rocha, Daniela N., Carvalho, Eva D., Pêgo, Ana Paula
• Format: Article
• Language: English
• Subjects: Animals; Cell Culture Techniques; High-Throughput Screening Assays; Humans; Neurodegenerative Diseases
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2016.05.005

•Simple and robust readout methods are crucial to the success of an HTS platform.•Molecular gradients are important regulatory components of tissue processes.•Mechanotransduction is becoming a relevant player in CNS disease.•3D neural cultures are expected to improve current in vitro models significantly.•A multidisciplinary approach will be key for the evolution of the HTS field. Despite the recent progress in the understanding of neurodegenerative disorders, a lack of solid fundamental knowledge on the etiology of many of the major neurodegenerative diseases has made it difficult to obtain effective therapies to treat these conditions. Scientists have been looking to carry out more-human-relevant studies, with strong statistical power, to overcome the limitations of preclinical animal models that have contributed to the failure of numerous therapeutics in clinical trials. Here, we identify currently existing platforms to mimic central nervous system tissues, healthy and diseased, mainly focusing on cell-based platforms and discussing their strengths and limitations in the context of the high-throughput screening of new therapeutic targets and drugs. Several cell-based platforms are being explored as central nervous system tissue mimics, in health and in disease, for the high-throughput screening of new therapeutic targets and drugs to address the challenging management of neurodegenerative disorders.