Delta(24)-sterol reductase (DHCR24) (DHCR24)

Delta(24)-sterol reductase (DHCR24), also known as Seladin-1, is a multifunctional enzyme that catalyzes the final step of cholesterol biosynthesis by reducing the delta-24 double bond of sterol intermediates like desmosterol (UniProt Q15392). It plays a critical role in cellular survival by regulating the formation and integrity of lipid rafts, which are cholesterol-rich membrane microdomains essential for signaling (PubMed: 24631365). Within these rafts, DHCR24 facilitates the recruitment and activation of the AKT (Protein Kinase B) signaling pathway, thereby promoting cell proliferation and protecting against apoptosis (PubMed: 18252123). In neurodegenerative diseases such as Alzheimer's, DHCR24 expression is often downregulated, leading to increased vulnerability to oxidative stress and amyloid-beta toxicity (PubMed: 10859301). Conversely, its upregulation in various cancers, including prostate cancer and melanoma, drives oncogenic AKT signaling and contributes to tumor progression and therapy resistance (PubMed: 22430261). Pharmacological inhibitors like U18666A and azacosterol are used to study the effects of DHCR24 inhibition on cholesterol metabolism and downstream signaling pathways (PubChem CID 166958). Additionally, DHCR24 has been identified as a necessary host factor for the replication of the Hepatitis C virus, making it a target of interest in infectious disease research (PubMed: 21508233).

Other names

Seladin-124-dehydrocholesterol reductaseDesmosterol-delta24-reductaseSELADIN1Selective AD indicator 1

Inhibition of the reduction of the C24-25 double bond in sterol intermediates, leading to the accumulation of desmosterol and the disruption of cholesterol-rich lipid rafts, which subsequently impairs the recruitment and phosphorylation of AKT.