{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n COL25A1, also known as CLAC‐P, is a collagenous type II transmembrane protein selectively expressed in neurons. Studies have demonstrated that COL25A1 binds aggregated amyloid‐β (Aβ) peptides, thereby promoting their deposition into senile plaques, modulating plaque structure, and increasing resistance to proteolytic degradation. These actions are thought to contribute to Alzheimer’s disease (AD) pathogenesis, as overexpression of COL25A1 in transgenic mice upregulates AD‐related proteins such as BACE1 and p35/p25, which in turn leads to intracellular Aβ aggregation, synaptic alterations, and astrocyte activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in AD, COL25A1 is essential for proper neuromuscular connectivity. Loss‐of‐function studies in mice have revealed that absence of COL25A1 disrupts intramuscular motor innervation and myoblast fusion, leading to halted motor axon extension, neuronal apoptosis, and immature skeletal muscle development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, mutations in COL25A1 have been associated with congenital cranial dysinnervation disorders and isolated congenital ptosis, underscoring a key role in ocular motor development and extraocular muscle innervation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": " Copy number alterations affecting COL25A1 have also been linked with broader developmental delays and behavioral abnormalities."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that COL25A1 functions as a multifunctional protein, integrating its role in amyloid plaque formation and neurodegeneration with essential processes in neuromuscular and ocular motor development. Its diverse functions make COL25A1 a promising therapeutic target for both Alzheimer’s disease and congenital neuromuscular disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ying Tong, Ying Xu, Kimberly Scearce-Levie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "COL25A1 triggers and promotes Alzheimer's disease-like pathology in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurogenetics (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10048-009-0201-5"}], "href": "https://doi.org/10.1007/s10048-009-0201-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19548013"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19548013"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yoshihide Osada, Tadafumi Hashimoto, Akiko Nishimura, et al. 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