| Autor: |
Tian M, Kawaguchi R, Shen Y, Machnicki M, Villegas NG, Cooper DR, Montgomery N, Haring J, Lan R, Yuan AH, Williams CK, Magaki S, Vinters HV, Zhang Y, De Biase LM, Silva AJ, Carmichael ST |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 27. Date of Electronic Publication: 2024 Mar 27. |
| DOI: |
10.1101/2024.03.24.585301 |
| Abstrakt: |
Vascular dementia (VaD) is a white matter ischemic disease and the second-leading cause of dementia, with no direct therapy. Within the lesion site, cell-cell interactions dictate the trajectory towards disease progression or repair. To elucidate the underlying intercellular signaling pathways, a VaD mouse model was developed for transcriptomic and functional studies. The mouse VaD transcriptome was integrated with a human VaD snRNA-Seq dataset. A custom-made database encompassing 4053 human and 2032 mouse ligand-receptor (L-R) interactions identified significantly altered pathways shared between human and mouse VaD. Two intercellular L-R systems, Serpine2-Lrp1 and CD39-A3AR, were selected for mechanistic study as both the ligand and receptor were dysregulated in VaD. Decreased Seprine2 expression enhances OPC differentiation in VaD repair. A clinically relevant drug that reverses the loss of CD39-A3AR function promotes tissue and behavioral recovery in the VaD model. This study presents novel intercellular signaling targets and may open new avenues for VaD therapies. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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