PIAS3 suppresses damage in an Alzheimer’s disease cell model by inducing the STAT3-associated STAT3/Nestin/Nrf2/HO-1 pathway

Molecular Medicine

Qiaoya Ma¹  Chen Li¹  Youyou Zhang¹  Ruili Wang¹  Chunting Hu¹ 

[1] Department of Geriatrics Neurology, the Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwu Road, 710004, Xi’an, Shaanxi, People’s Republic of China;

关键词: Alzheimer’s disease;    Aβ;    PIAS3;    STAT3;    Oxidative;    Apoptosis;   

DOI  :  10.1186/s10020-021-00410-3

来源: Springer

【 摘 要 】

BackgroundAlzheimer’s disease (AD), the most common form of dementia, is caused by the degeneration of the central nervous system (CNS). A previous study reported that signal transducer and activator of transcription 3 (STAT3) is activated during AD development; nonetheless, the related mechanism remains unknown. Thus, this study used a cell model to explore whether and how the protein inhibitor of activated STAT3 (PIAS3) is involved in AD development.MethodsCerebrospinal fluid (CSF) specimens of 30 patients with AD and 10 normal participants were included in this study. SH-SY5Y cells were used to constructed AD model. Relevant indices were then detected and analyzed.ResultsThe results showed that compared with the control group, PIAS3 expression was substantially decreased in patients with AD and amyloid beta (Aβ)-treated SH-SY5Y cells. PIAS3 overexpression was able to reverse the detrimental effects of Aβ treatment on cell survival and growth. Further, it could also ameliorate apoptosis and oxidative stress in Aβ-treated SH-SY5Y cells. Additionally, PIAS3 was shown to reduce the activated form of STAT3 and increase the activity of the downstream Nestin/nuclear factor erythroid 2-related factor/heme oxygenase-1 pathway.ConclusionsSTAT3 reactivation by colivelin treatment negated the influence of PIAS3 on the survival, growth, apoptosis, and oxidative stress of Aβ-treated SH-SY5Y cells.

【 授权许可】

CC BY