PCSK1N Human

Proprotein Convertase Subtilisin/Kexin Type 1 Inhibitor, commonly referred to as PCSK1N or proSAAS, is a protein encoded by the PCSK1N gene in humans . This protein plays a crucial role in the regulation of the neuroendocrine secretory pathway and is predominantly expressed in cells with a regulated secretory pathway, such as endocrine and neuroendocrine cells .

The PCSK1N gene is located on the X chromosome (Xp11.23) in humans . The gene encodes a protein that undergoes further processing into multiple short peptides . The intact proSAAS protein, as well as its carboxy-terminal peptide containing the inhibitory hexapeptide LLRVKR, functions as an inhibitor of prohormone convertase 1/3 (PC1/3), which is responsible for the initial proteolytic cleavage of peptide precursors .

ProSAAS is expressed largely in cells possessing a regulated secretory pathway, such as endocrine/neuroendocrine cells and neurons . The protein functions as an inhibitor of prohormone convertase 1/3 (PC1/3), which is crucial for the proteolytic cleavage of peptide precursors . This inhibition is significant because it regulates the processing of neuroendocrine peptide precursors, thereby influencing various physiological processes .

The central, unprocessed portion of the proSAAS protein may function as a neural- and endocrine-specific chaperone due to its potent ability to block the aggregation of beta-amyloid and alpha-synuclein in vitro, and to block oligomer cytotoxicity in cells . Recent data suggest that nigral proSAAS expression can block the deterioration of the striatonigral pathway in a synuclein rat model of Parkinson’s disease .

Differential expression of the PCSK1N gene has been associated with obesity . Additionally, the protein’s ability to inhibit the aggregation of beta-amyloid and alpha-synuclein suggests potential therapeutic applications in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease .