| First Author | Xing ZK | Year | 2023 |
| Journal | Neural Regen Res | Volume | 18 |
| Issue | 6 | Pages | 1300-1307 |
| PubMed ID | 36453415 | Mgi Jnum | J:350142 |
| Mgi Id | MGI:7662476 | Doi | 10.4103/1673-5374.358607 |
| Citation | Xing ZK, et al. (2023) The relationship among amyloid-beta deposition, sphingomyelin level, and the expression and function of P-glycoprotein in Alzheimer's disease pathological process. Neural Regen Res 18(6):1300-1307 |
| abstractText | In Alzheimer's disease, the transporter P-glycoprotein is responsible for the clearance of amyloid-beta in the brain. Amyloid-beta correlates with the sphingomyelin metabolism, and sphingomyelin participates in the regulation of P-glycoprotein. The amyloid cascade hypothesis describes amyloid-beta as the central cause of Alzheimer's disease neuropathology. Better understanding of the change of P-glycoprotein and sphingomyelin along with amyloid-beta and their potential association in the pathological process of Alzheimer's disease is critical. Herein, we found that the expression of P-glycoprotein in APP/PS1 mice tended to increase with age and was significantly higher at 9 and 12 months of age than that in wild-type mice at comparable age. The functionality of P-glycoprotein of APP/PS1 mice did not change with age but was significantly lower than that of wild-type mice at 12 months of age. Decreased sphingomyelin levels, increased ceramide levels, and the increased expression and activity of neutral sphingomyelinase 1 were observed in APP/PS1 mice at 9 and 12 months of age compared with the levels in wild-type mice. Similar results were observed in the Alzheimer's disease mouse model induced by intracerebroventricular injection of amyloid-beta1-42 and human cerebral microvascular endothelial cells treated with amyloid-beta1-42. In human cerebral microvascular endothelial cells, neutral sphingomyelinase 1 inhibitor interfered with the changes of sphingomyelin metabolism and P-glycoprotein expression and functionality caused by amyloid-beta1-42 treatment. Neutral sphingomyelinase 1 regulated the expression and functionality of P-glycoprotein and the levels of sphingomyelin and ceramide. Together, these findings indicate that neutral sphingomyelinase 1 regulates the expression and function of P-glycoprotein via the sphingomyelin/ceramide pathway. These studies may serve as new pursuits for the development of anti-Alzheimer's disease drugs. |
