Research Progress in the Pathogenic Mechanism and Treatment Strategies of DHCR24 in Diseases
ZHANG Fan1, WEI Jiale1,2, XIONG Yang1,2*
DHCR24 (dehydrocholesterol reductase 24), known as Seladin-1 (selective Alzheimer’s disease indicator-1), a key enzyme in the cholesterol synthesis pathway, catalyzes the reduction of Δ24 double bond in sterol intermediate to produce cholesterol. Initially, DHCR24 was regarded as an anti-apoptotic factor due to its abnormal expression during the pathological process of AD (Alzheimer’s disease) and its demonstrated neuroprotective properties. Recent studies have shown that regulated by aberrant DNA methylation and different hormones, DHCR24 not only participates in the pathological process of AD, but also shows abnormal expression in the neurodegenerative diseases (Huntington’s disease), metabolic-related diseases (diabetes mellitus), and various solid tumors (prostate cancer, hepatocellular carcinoma, bladder cancer, melanoma, breast cancer, etc.). The relevant mechanisms of DHCR24 include (1) dysfunction of cholesterol synthesis; (2) anti-apoptotic function or induction of cytotoxicity. Consequently, current research has developed DHCR24 inhibitors (including U18666A, SH42, etc.) and activators [including lipid extracts of Asian brown seaweeds Sargassum fusiforme, TMP (tetramethylpyrazine) from Chuanxiong]. This review summarizes the pathogenic mechanisms and treatment strategies of DHCR24 in the hopes of providing reference for research and treatment of diseases.
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