{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that membrane proteins with leucine‐rich repeat and immunoglobulin‐like domains play multifaceted roles in neural survival and connectivity. For instance, a Ca2⁺‐dependent primary response gene (ali1) is transcriptionally activated by neuronal activity and Ca2⁺ influx, thereby promoting depolarization‐dependent survival of neurons."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, AMIGO2—a downstream target of calcium‐dependent survival signals—displays a highly specific expression pattern in the hippocampus that aligns with regions known to resist neurotoxicity, suggesting its involvement in neuroprotection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, in the retina AMIGO2 acts as a dendritic scaling factor, precisely regulating the arbor size of starburst amacrine and rod bipolar cells to ensure proper visual feature detection, while its selective expression in the medial habenula implicates it in controlling axonal fasciculation and pathway organization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond the nervous system, AMIGO2 has emerged as a pivotal regulator of tumor progression. Its overexpression promotes the adhesion of tumor cells to liver endothelial cells, thereby driving liver metastasis in fibrosarcoma models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Similarly, in samples derived from metastatic breast cancers, AMIGO2 was identified as a driver of cell invasion whose high expression correlates with decreased relapse‐free survival, implicating it as a potential marker of aggressive disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, AMIGO2 plays important roles in modulating immune and cardiovascular functions. In T cells, AMIGO2 influences migratory behavior, activation status, and cytokine production; its deficiency in experimental models of autoimmune encephalomyelitis leads to reduced central nervous system T‐cell accumulation and mitigated disease severity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Preliminary investigations also suggest that AMIGO2 may be involved in the pathogenesis of myocardial infarction, hinting at broader therapeutic implications in ischemic heart disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tomio Ono, Naoko Sekino-Suzuki, Yoshiaki Kikkawa, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Loss of AMIGO2 causes dramatic damage to cardiac preservation after ischemic injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiol J (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.5603/CJ.a2018.0049"}], "href": "https://doi.org/10.5603/CJ.a2018.0049"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29718531"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29718531"}]}]}]}