Acid sphingomyelinase-mediated blood-brain barrier disruption in aging

Min Hee Park, Hee Kyung Jin, Jae Sung Bae

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Although many studies have reported that the breakdown of the blood-brain barrier (BBB) represents one of the major pathological changes in aging, the mechanism underlying this process remains relatively unexplored. In this study, we described that acid sphingomyelinase (ASM) derived from endothelial cells plays a critical role in BBB disruption in aging. ASM levels were elevated in the brain endothelium and plasma of aged humans and mice, resulting in BBB leakage through an increase in caveolae-mediated transcytosis. Moreover, ASM caused damage to the caveolae-cytoskeleton via protein phosphatase 1-mediated ezrin/radixin/moesin dephosphorylation in primary mouse brain endothelial cells. Mice overexpressing brain endothelial cell-specific ASM exhibited acceleration of BBB impairment and neuronal dysfunction. However, genetic inhibition and endothelial specific knock-down of ASM in mice improved BBB disruption and neurocognitive impairment during aging. Results of this study revealed a novel role of ASM in the regulation of BBB integrity and neuronal function in aging, thus highlighting the potential of ASM as a new therapeutic target for anti-aging.

Original languageEnglish
Pages (from-to)111-112
Number of pages2
JournalBMB Reports
Issue number2
StatePublished - 2019
Externally publishedYes


  • Acid sphingomyelinase
  • Aging
  • Blood-brain barrier
  • Caveolae
  • Endothelial cell


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