TY - JOUR
T1 - Neurodevelopmental disorders, immunity, and cancer are connected
AU - Nussinov, Ruth
AU - Tsai, Chung Jung
AU - Jang, Hyunbum
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/6/17
Y1 - 2022/6/17
N2 - 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.
AB - 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.
KW - Biophysics
KW - Cancer
KW - Immunology
KW - Neuroscience
UR - http://www.scopus.com/inward/record.url?scp=85131723936&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2022.104492
DO - 10.1016/j.isci.2022.104492
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C2 - 35712080
AN - SCOPUS:85131723936
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 6
M1 - 104492
ER -