Molecular Systems Biology of Neurodevelopmental Disorders, Rett Syndrome as an Archetype

Frontiers in Integrative Neuroscience
Victor FaundezDaniel Charles Tarquinio

Abstract

Neurodevelopmental disorders represent a challenging biological and medical problem due to their genetic and phenotypic complexity. In many cases, we lack the comprehensive understanding of disease mechanisms necessary for targeted therapeutic development. One key component that could improve both mechanistic understanding and clinical trial design is reliable molecular biomarkers. Presently, no objective biological markers exist to evaluate most neurodevelopmental disorders. Here, we discuss how systems biology and "omic" approaches can address the mechanistic and biomarker limitations in these afflictions. We present heuristic principles for testing the potential of systems biology to identify mechanisms and biomarkers of disease in the example of Rett syndrome, a neurodevelopmental disorder caused by a well-defined monogenic defect in methyl-CpG-binding protein 2 (MECP2). We propose that such an approach can not only aid in monitoring clinical disease severity but also provide a measure of target engagement in clinical trials. By deepening our understanding of the "big picture" of systems biology, this approach could even help generate hypotheses for drug development programs, hopefully resulting in new treatments for these ...Continue Reading

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Citations

Apr 17, 2021·Expert Review of Proteomics·Daniela BraconiAnnalisa Santucci
Jul 3, 2021·Life·Alessandra PecorelliGiuseppe Valacchi
Jul 13, 2021·Frontiers in Cellular Neuroscience·Andres Di PaoloJosé Roberto Sotelo-Silveira
Aug 28, 2021·Genes·William Fyke, Milen Velinov

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Methods Mentioned

BETA
biopsies
immunoprecipitation
ChIP
acetylation
Human Genome Sequencing

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