Neurodevelopmental disorders, immunity, and cancer are connected

Ruth Nussinov*, Chung Jung Tsai, Hyunbum Jang

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations

Abstract

Immunity could be viewed as the common factor in neurodevelopmental disorders and cancer. The immune and nervous systems coevolve as the embryo develops. Immunity can release cytokines that activate MAPK signaling in neural cells. In specific embryonic brain cell types, dysregulated signaling that results from germline or embryonic mutations can promote changes in chromatin organization and gene accessibility, and thus expression levels of essential genes in neurodevelopment. In cancer, dysregulated signaling can emerge from sporadic somatic mutations during human life. Neurodevelopmental disorders and cancer share similarities. In neurodevelopmental disorders, immunity, and cancer, there appears an almost invariable involvement of small GTPases (e.g., Ras, RhoA, and Rac) and their pathways. TLRs, IL-1, GIT1, and FGFR signaling pathways, all can be dysregulated in neurodevelopmental disorders and cancer. Although there are signaling similarities, decisive differentiating factors are timing windows, and cell type specific perturbation levels, pointing to chromatin reorganization. Finally, we discuss drug discovery.

Original languageEnglish
Article number104492
JournaliScience
Volume25
Issue number6
DOIs
StatePublished - 17 Jun 2022

Funding

FundersFunder number
U.S. Government
National Institutes of HealthHHSN261201500003I
U.S. Department of Health and Human Services
National Cancer Institute

    Keywords

    • Biophysics
    • Cancer
    • Immunology
    • Neuroscience

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