PreproNPY

Prepro-NPY, or preproNPY, is the precursor polypeptide that gives rise to neuropeptide Y (NPY), a highly conserved signaling molecule involved in a range of physiological processes. In humans and other vertebrates, prepro-NPY is encoded by the NPY gene. The encoded protein contains an N-terminal signal peptide that directs it into the secretory pathway, followed by a propeptide region and the C-terminal neuropeptide Y sequence. Through proteolytic processing, the signal peptide is removed to form pro-NPY, which is then cleaved by proprotein convertases and related peptidases to generate mature NPY.

Mature NPY is a small peptide that exerts its effects by binding to several G protein–coupled receptors, principally Y1, Y2, Y4, and Y5. Activation of these receptors modulates neurotransmission and regulates numerous physiological functions, notably feeding behavior and energy homeostasis. The NPY system is especially enriched in the hypothalamus, where it plays a central role in stimulating appetite and influencing energy expenditure, while also participating in stress responses, circadian regulation, and autonomic control.

Expression and processing of prepro-NPY are influenced by nutritional status, hormonal signals, and neuronal activity. Dysregulation of the NPY/prepro-NPY system has been implicated in metabolic disorders, obesity susceptibility, anxiety, and mood regulation in various species. Ongoing research aims to clarify the precise regulatory mechanisms controlling prepro-NPY expression and how NPY signaling integrates metabolic and behavioral states.