Prion protein gene promoter (PRNP promoter) (PRNP promoter)

The Prion protein gene promoter (PRNP promoter) is the regulatory DNA sequence that initiates and controls the transcription of the PRNP gene, which encodes the cellular prion protein (PrPC) (Mahal et al., 2001). PrPC is a cell-surface glycoprotein expressed most abundantly in the brain and is essential for the pathogenesis of prion diseases, such as Creutzfeldt-Jakob disease and Bovine Spongiform Encephalopathy. In these conditions, PrPC undergoes a conformational change into a misfolded, infectious isoform known as PrPSc, which aggregates and causes neurodegeneration. Since the absence of PrPC confers resistance to prion infection, the PRNP promoter is a high-priority target for therapeutic silencing (Raymond et al., 2014). Strategies targeting the promoter include the use of CRISPR-based transcriptional repressors and small molecules that interfere with transcription factor binding sites, such as those for SP1 or HSF1 (Mercer et al., 2022). By reducing the expression of the PRNP gene at the transcriptional level, these therapies aim to lower the overall concentration of PrPC, thereby limiting the substrate available for conversion into the toxic PrPSc form. However, therapeutic development must account for the potential loss of PrPC's physiological roles, such as its involvement in peripheral nerve myelin maintenance (Bremer et al., 2010).

Other names

PRNP promoterPrP promoterPrion protein promoterCD230 promoterPrnp promoterPRNP gene regulatory region

Transcriptional repression or silencing of the PRNP gene to reduce the expression of cellular prion protein (PrPC), thereby limiting the substrate for conversion into the pathogenic PrPSc isoform.