Collagen type XXV alpha-1 chain (COL25A1)

Collagen type XXV alpha-1 chain (COL25A1) is a brain-specific, membrane-associated collagen uniquely expressed in neurons. It is classified as a type II transmembrane protein and features three collagenous domains (COL1–3) flanked by four noncollagenous domains (NC1–4). COL25A1 undergoes proteolytic processing to produce the fragment CLAC (collagenous Alzheimer amyloid plaque component), which specifically binds amyloid-beta peptides found in Alzheimer’s disease plaques. Unlike many other plaque-associated proteins, CLAC inhibits elongation of amyloid fibrils but can also organize amyloid into more protease-resistant aggregates. Overexpression of COL25A1 in animal models induces Alzheimer’s disease-like pathology, increases levels of BACE1 (beta-site APP cleaving enzyme 1), promotes amyloid accumulation, disrupts synaptic markers, and induces local inflammatory responses, supporting a pathogenic role in neurodegeneration. COL25A1 is also implicated in congenital fibrosis syndromes affecting extraocular muscles. Although it interacts with amyloid-beta and affects its aggregation, specific drugs targeting COL25A1 are not established. Modulation of its activity may represent a future therapeutic strategy for Alzheimer’s disease[1][2].

Other names

Collagen alpha-1(XXV) chainCollagen-like Alzheimer amyloid plaque componentCOL25A1AMYCLACAlzheimer disease amyloid-associated proteinCLAC-PCLACPcollagenous Alzheimer amyloid plaque componentCFEOM5

Not established in clinical pharmacology; modulation of amyloid-beta aggregation and fibril formation may represent a conceptual therapeutic mechanism