Targeting Neuropeptide Y: Novel Approaches to the Treatment of Cardiovascular and Haematological Disorders

BACKGROUND: The 36-amino acid peptide known as neuropeptide Y (NPY) is widely expressed in both the central and peripheral nerve systems and is essential for regulating energy balance, stress responses, cardiovascular function, and immunological regulation through Gprotein- coupled Y receptors (Y1, Y2, Y4, Y5). OBJECTIVE: To explore the various functions of NPY in hematological and cardiovascular disorders and investigate potential therapeutic approaches that target NPY signaling networks. METHODS: A comprehensive literature analysis focused on NPY-mediated mechanisms in cardiovascular diseases (CVDs) and hematological disorders. The review highlights pharmacological modulators, including synthetic analogs, receptor-specific agents, enzyme inhibitors, and natural substances. RESULTS: NPY dysregulation promotes vasoconstriction and inflammation, particularly through Y1 receptor activation, contributing to diseases such as atherosclerosis, heart failure, and hypertension. In hematological disorders, NPY influences hematopoiesis, immune cell activity, and angiogenesis, affecting conditions such as thrombosis and leukemia. Therapeutic approaches include receptor-specific agonists and antagonists (e.g., [Leu31, Pro34]NPY, BAY 53-6206), enzyme inhibitors (DPP4, NEP), and natural substances (flavonoids, polyphenols, saponins). Although therapeutic resistance remains a challenge, glucocorticoids also affect NPY expression. CONCLUSION: NPY acts as a crucial modulator in hematological and cardiovascular disorders. Understanding its receptor-specific functions enables the development of targeted therapeutic strategies. Natural substances provide promising adjuncts for modulating NPY activity, supporting integrated approaches for treating NPY-related disorders.