Nrg1 Intracellular Signaling Is Neuroprotective upon Stroke
NRG1 phylogenetic conservation and expression in aging. (a) Sequence alignment of the transmembrane and intracellular regions of NRG1 that are crucial for intracellular signaling, namely, the transmembrane domain (in light-blue), the nuclear localization signal (in red), and the phosphorylation sites (green circles). The black arrowhead indicates the location of the Val-to-Leu (rs7494201) schizophrenia-linked mutation that affects gamma-secretase processing and Nrg1 intracellular signaling. The red arrowheads indicate the amino acids in the nuclear localization signal required for the nuclear targeting of Nrg1-ICD. The grey arrowhead indicates the site of the Met-to-Thr mutation, rs10503929, while the white arrowhead indicates a primate-specific polymorphism. CRD: cysteine-rich domain; EGF: epithelial growth factor domain; TM: transmembrane domain. (b) Forest plot showing the correlation -score between age and mRNA expression for NRG1 and ERBB4 in four independent datasets (Tgen, ; BrainEqtl, ; HBTRC, ; BrainCloud, ). Meta-analysis conducted at the gene level employing Stouffer’s weighted -score.
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