Vascular and Neurogenic Rejuvenation in Aging Mice by Modulation of ASM
- Title
- Vascular and Neurogenic Rejuvenation in Aging Mice by Modulation of ASM
- Author
- 김희진
- Keywords
- BLOOD-BRAIN-BARRIER; ACID SPHINGOMYELINASE/CERAMIDE PATHWAY; CAVEOLAE-MEDIATED TRANSCYTOSIS; ALZHEIMERS-DISEASE; PERMEABILITY; CELLS; CYTOSKELETON; DYSFUNCTION; DISRUPTION; MECHANISMS
- Issue Date
- 2018-10
- Publisher
- CELL PRESS
- Citation
- NEURON, v. 100, no. 1, page. 167-182.e9
- Abstract
- Although many reports have revealed dysfunction of endothelial cells in aging, resulting in blood-brain barrier (BBB) breakdown, the underlying mechanism or mechanisms remain to be explored. Here, we find that acid sphingomyelinase (ASM) is a critical factor for regulating brain endothelial barrier integrity. ASM is increased in brain endothelium and/or plasma of aged humans and aged mice, leading to BBB disruption by increasing caveolae-mediated transcytosis. Genetic inhibition and endothelial-specific knockdown of ASM in mice ameliorated BBB breakdown and neurocognitive impairment during aging. Using primary mouse brain endothelial cells, we found that ASM regulated the caveolae-cytoskeleton interaction through protein phosphatase 1-mediated ezrin/radixin/moesin (ERM) dephosphorylation and apoptosis. Moreover, mice with conditional ASM overexpression in brain endothelium accelerated significant BBB impairment and neurodegenerative change. Overall, these results reveal a novel role for ASM in the control of neurovascular function in aging, suggesting that ASM may represent a new therapeutic target for anti-aging.
- URI
- https://www.cell.com/neuron/fulltext/S0896-6273(18)30783-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0896627318307839%3Fshowall%3Dtruehttps://repository.hanyang.ac.kr/handle/20.500.11754/120327
- ISSN
- 0896-6273; 1097-4199
- DOI
- 10.1016/j.neuron.2018.09.010
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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