The potential role of transcription factor sterol regulatory element binding proteins (SREBPs) in Alzheimer's disease

Abstract

Sterol regulatory element binding proteins (SREBPs) are a series of cholesterol-related transcription factors. Their role in regulating brain cholesterol biosynthesis, amyloid accumulation, and tau tangles formation has been intensively studied in protein-protein interaction analysis based on genes in clinical databases. SREBPs play an important role in maintaining cholesterol homeostasis in the brain. There are three subtypes of SREBPs, SREBP-1a stimulates the expression of genes related to cholesterol and fatty acid synthesis, SREBP-1c stimulates adipogenesis, and SREBP-2 stimulates cholesterol synthase and LDL receptors. SREBP-2 is activated in response to cholesterol depletion and stimulates a compensatory upregulation of cholesterol uptake and synthesis. Previous studies have shown that inhibition of SREBP-2 reduces cholesterol and amyloid accumulation, and new research suggests that SREBPs play a multifaceted role in Alzheimer's disease. Here, we highlight the importance of SREBPs in AD, in terms of multiple pathways regulating cholesterol in the brain, and primarily demonstrate the potential of SREBP-2 inhibitors. There was a trend towards a significant increase in the expression levels of different SREBP isoforms in AD patients compared to healthy controls. Therefore, there is a close link between SREBPs and AD, and this review analyses the potential role of SREBPs in the treatment of AD. In addition, we systematically reviewed the research progress of SREBPs in AD, and this review will provide more innovative insights into the pathogenesis and treatment of AD and new strategies for drug development in AD.