Neuropeptide Y Crosstalk: in Health and Disease

Abstract

Neuropeptide Y (NPY) is a multifunctional peptide that plays a significant role in various physiological processes, including energy balance, appetite regulation, cardiovascular function, immune modulation, and stress response. This manuscript provides an extensive review of NPY’s mechanisms of action and its therapeutic potential across multiple biological systems. NPY exerts its effects primarily through five G-protein-coupled receptors: Y1, Y2, Y4, Y5, and Y6, each contributing uniquely to distinct physiological outcomes.

The Y1 receptor is extensively involved in appetite stimulation, vasoconstriction, and anxiety modulation, while the Y2 receptor primarily regulates neurotransmitter release and energy homeostasis. Notably, the Y4 receptor plays a critical role in regulating pancreatic secretions, gut motility, and appetite, making it a potential target for managing metabolic disorders and digestive health. On the other hand, the Y5 receptor is key in stimulating appetite and increasing energy intake and body weight, highlighting its significance in obesity and weight management therapies.

NPY's cardiovascular effects, such as blood pressure regulation and heart rate modulation, underscore its potential in treating conditions like hypertension and heart failure. Additionally, NPY demonstrates neuroprotective properties by supporting neuronal survival, enhancing synaptic plasticity, and mitigating neuroinflammation, which positions it as a promising candidate for therapeutic strategies in neurodegenerative diseases like Alzheimer's and Parkinson's. Its ability to reduce anxiety and enhance stress resilience further extends its therapeutic potential to mental health disorders.

In the context of periodontal disease, NPY influences inflammatory responses, bone metabolism, and tissue remodeling, underscoring its role in both systemic and localized disease management. This comprehensive review emphasizes the diverse roles of NPY and its receptors, advocating for further research to fully explore their clinical applications and optimize therapeutic strategies for a range of health conditions.