Longevity & AgingBrain Protein HAPLN2 Aggregates With Age and Fuels Neuroinflammation
Researchers identified HAPLN2, a hyaluronic acid-binding extracellular matrix protein found at nodes of Ranvier, as a novel age-dependent aggregating protein in mouse brains. Using sarkosyl-insolubility fractionation and mass spectrometry, the team showed HAPLN2 accumulates progressively with age, driven by rising hyaluronic acid levels and declining microglial clearance capacity. HAPLN2 oligomers directly triggered inflammatory responses in microglia both in cell culture and in living animals. Critically, age-associated HAPLN2 aggregation was also confirmed in human cerebellar tissue, suggesting translational relevance. The findings position HAPLN2 as a novel contributor to neuroinflammatory brain aging, even in the absence of classical neurodegenerative disease.
