SIRT7 Deficiency Protects against Aβ42-Induced Apoptosis through the Regulation of NOX4-Derived Reactive Oxygen Species Production in SH-SY5Y Cells

• DOI: 10.3390/ijms23169027
• Publication Date: 2022-08-15T05:47:21Z
• Authors: Hironori Mizutani; Yoshifumi Sato; Masaya Yamazaki; Tatsuya Yoshizawa; Yukio Ando; Mitsuharu Ueda; Kazuya Yamagata
• Keywords: 0301 basic medicine; Amyloid beta-Peptides; SIRT7; Alzheimer’s disease; amyloid-β; apoptosis; reactive oxygen species; NADPH oxidase; Apoptosis; Neurodegenerative Diseases; Article; Peptide Fragments; Neuroblastoma; 03 medical and health sciences; Alzheimer Disease; NADPH Oxidase 4; Cell Line, Tumor; Humans; Sirtuins; Reactive Oxygen Species

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is characterized by irreversible memory loss and cognitive decline. The deposition of amyloid-β (Aβ), especially aggregation-prone Aβ42, is considered to be an early event preceding neurodegeneration in AD. Sirtuins (SIRT1–7 in mammals) are nicotinamide adenine dinucleotide-dependent lysine deacetylases/deacylases, and several sirtuins play important roles in AD. However, the involvement of SIRT7 in AD pathogenesis is not known. Here, we demonstrate that SIRT7 mRNA expression is increased in the cortex, entorhinal cortex, and prefrontal cortex of AD patients. We also found that Aβ42 treatment rapidly increased NADPH oxidase 4 (NOX4) expression at the post-transcriptional level, and induced reactive oxygen species (ROS) production and apoptosis in neuronal SH-SY5Y cells. In contrast, SIRT7 knockdown inhibited Aβ42-induced ROS production and apoptosis by suppressing the upregulation of NOX4. Collectively, these findings suggest that the inhibition of SIRT7 may play a beneficial role in AD pathogenesis through the regulation of ROS production.