| First Author | Wang J | Year | 2021 |
| Journal | Neurosci Lett | Volume | 744 |
| Pages | 135598 | PubMed ID | 33373677 |
| Mgi Jnum | J:303852 | Mgi Id | MGI:6509917 |
| Doi | 10.1016/j.neulet.2020.135598 | Citation | Wang J, et al. (2021) PGC-1alpha reduces Amyloid-beta deposition in Alzheimer's disease: Effect of increased VDR expression. Neurosci Lett 744:135598 |
| abstractText | Amyloid-beta (Abeta) is the core component of amyloid plaques of Alzheimer's disease (AD). Recent evidence has confirmed that Abeta triggers neurodegeneration by dramatically suppressing vitamin D receptor (VDR) expression. Thus far, the onset mechanisms and means of preventing AD are largely unknown. Perioxisome proliferator-activated receptor-gamma coactivator (PGC-1alpha), as a transcriptional coactivator of VDR could protect cells against oxidative stress. Thus, upregulation of PGC-1alpha is a candidate therapeutic strategy for AD. To investigate the effect of PGC-1alpha in AD, and to illuminate the precise involvement of VDR in the neuroprotective strategy, the varies of molecular of PGC-1alpha and VDR were studied in APP/PS-1 double transgenic (2xTg-AD) mice at 6 months of age, significant reduction in the expression of PGC-1alpha and VDR was found in their hippocampus and the cortex. Besides, a specific mouse line, Dlx5/6-Cre:PGC-1alpha(fl/fl) in which the PGC-1alpha deficiency was limited to the hippocampus and the cortex, was used to study the target intervention of PGC-1alpha, decreased expression of VDR and increased oxidative damage were observed in AD-related brain regions by PGC-1alpha deficiency. To explore the function and therapeutic strategy of PGC-1alpha in AD, an adeno-associated virus (AAV) was used to induce PGC-1alpha overexpressed in the hippocampus of 2xTg-AD mice. Overexpressed PGC-1alpha results in a remarkable increase in the levels of VDR associated with a significant reduction in the expression of Abeta plaques and of 8-oxo-dG in 2xTg-AD mice. These data may have ramifications for neuroprotective strategies targeting overexpression of PGC-1alpha in Alzheimer's disease. |
