Amyloid-β (Aβ) is the core component of amyloid plaques of Alzheimer's disease (AD). Recent evidence has confirmed that Aβ 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-γ coactivator (PGC-1α), as a transcriptional coactivator of VDR could protect cells against oxidative stress. Thus, upregulation of PGC-1α is a candidate therapeutic strategy for AD. To investigate the effect of PGC-1α in AD, and to illuminate the precise involvement of VDR in the neuroprotective strategy, the varies of molecular of PGC-1α 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-1α and VDR was found in their hippocampus and the cortex. Besides, a specific mouse line, Dlx5/6-Cre:PGC-1α^fl/fl in which the PGC-1α deficiency was limited to the hippocampus and the cortex, was used to study the target intervention of PGC-1α, decreased expression of VDR and increased oxidative damage were observed in AD-related brain regions by PGC-1α deficiency. To explore the function and therapeutic strategy of PGC-1α in AD, an adeno-associated virus (AAV) was used to induce PGC-1α overexpressed in the hippocampus of 2xTg-AD mice. Overexpressed PGC-1α results in a remarkable increase in the levels of VDR associated with a significant reduction in the expression of Aβ plaques and of 8-oxo-dG in 2xTg-AD mice. These data may have ramifications for neuroprotective strategies targeting overexpression of PGC-1α in Alzheimer's disease.

淀粉样蛋白-β（Aβ）是阿尔茨海默氏病（AD）的淀粉样蛋白斑的核心成分。最近的证据证实，Aβ通过显着抑制维生素D受体（VDR）的表达来触发神经变性。迄今为止，预防AD的发病机制和手段在很大程度上是未知的。过氧化物酶体增殖物激活受体-γ共激活物（PGC-1α），作为VDR的转录共激活物，可以保护细胞免受氧化应激。因此，PGC-1α的上调是AD的候选治疗策略。为了研究PGC-1α在AD中的作用，并阐明VDR在神经保护策略中的确切参与，在APP / PS-1双转基因（2xTg-AD）小鼠中研究了PGC-1α和VDR的分子变化在6个月大时，在海马和皮层中发现PGC-1α和VDR的表达显着降低。此外，特定的小鼠系Dlx5 / 6-Cre：PGC-1α^{F / fl}中的PGC-1α缺陷仅限于海马和皮层，用于研究PGC-1α的目标干预，PGC-在AD相关脑区域观察到VDR表达降低和氧化损伤增加。 1α缺乏症。为了探讨PGC-1α在AD中的功能和治疗策略，使用腺相关病毒（AAV）诱导PGC-1α在2xTg-AD小鼠海马中过表达。在2xTg-AD小鼠中，过表达的PGC-1α导致VDR水平显着增加，与Aβ斑块和8-oxo-dG的表达显着降低有关。这些数据可能会对针对阿尔茨海默氏病中PGC-1α过表达的神经保护策略产生影响。