PPARγ coactivator-1α (PGC-1α) protects neuroblastoma cells against amyloid-beta (Aβ) induced cell death and neuroinflammation via NF-κB pathway

BMC Neuroscience

Research Article

Kai Wang¹  Yuqin Zhang²  Xiaoyu Wu³  Yanliu Jiang³  Changchun Chen³  Shupei Wang³ 

[1] Department of Neurology, The First Affiliated Hospital of Anhui Medical University, 230032, Hefei, Anhui, China;Department of Neurology, The First Affiliated Hospital of Anhui Medical University, 230032, Hefei, Anhui, China;Department of Neurology, The Second People’s Hospital of Anhui Province, 230011, Hefei, Anhui, China;Department of Neurology, The Second People’s Hospital of Anhui Province, 230011, Hefei, Anhui, China;

关键词: PGC-1α;    Aβ;    Neuronal death;    Neuroinflammation;    NF-κB pathway;   

DOI  :  10.1186/s12868-017-0387-7

 received in 2017-06-08, accepted in 2017-09-17,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAlzheimer’s disease is characterized by the accumulation of amyloid beta (Aβ) and the formation of neurofibrillary tangles. Aβ is the main constituent of senile plaques and is largely involved in neuronal death and neuroinflammation. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) is one of the main transcriptional coactivator and has been related to many fields such as energy metabolism, cardiovascular disease, neurodegenerative disorders, and so on.ResultsTreatment with Aβ1–42 reduced the expression of PGC-1α in both protein and RNA levels of neuroblastoma N2a cells. Aβ1–42 induced a robust activation of cleaved caspase-3 while PGC-1α suppressed this activation and protected N2a cells from Aβ-induced cell death. Overexpression of PGC-1α significantly reduced the level of main proinflammatory cytokines. In addition, PGC-1α inhibited the transportation of NF-κB p65 from cytoplasm to nucleus and IκBα degradation induced by Aβ1–42.ConclusionOur results have demonstrated that PGC-1α can protect neuroblastoma cells against Aβ-induced neuronal death and neuroinflammation. Moreover, this neuroprotective effect of PGC-1α is regulated through NF-κB pathway. Taken together, our work provides evidence that PGC-1α could be beneficial in targeting Aβ neurotoxicity.

【 授权许可】

CC BY   
© The Author(s) 2017