The neuropeptide Y (NPY) signaling pathway plays a central role in various physiological and pathological processes; its receptors are significant therapeutic targets, and NPY itself serves as a potential biomarker for several diseases.
Obesity and Metabolic Diseases
The NPY-Y1R/Y5R signaling pathway is a key mechanism driving appetite and weight gain, making it a crucial target for anti-obesity drug development. NPY acts as an appetite-stimulating factor. A 2024 study published in *Nature* revealed that peripheral NPY, produced by sympathetic nerves, exerts anti-obesity effects by maintaining thermogenic adipose tissue without altering food intake.
Neuropsychiatric Disorders
Individuals with lower brain levels of NPY are more prone to pessimism and depression. NPY possesses anxiolytic and antidepressant potential, and its levels are associated with anxiety and post-traumatic stress disorder (PTSD). A 2024 study in *Nature Communications* further highlighted the critical role of NPY neurons in the dorsal raphe nucleus and ventrolateral periaqueductal gray of the brainstem in counteracting stress-induced appetite loss and anxiety. Dysregulation of NPY signaling is also linked to nicotine addiction.
Neurodegenerative Diseases
In disease models of Alzheimer's, Parkinson's, and Huntington's diseases, NPY exhibits neuroprotective effects, though changes in its levels are disease-specific. For instance, hippocampal NPY levels are reduced in Alzheimer's patients, whereas striatal NPY levels are elevated in Parkinson's patients. NPY serves as both a potential biomarker and a therapeutic target for these neurodegenerative conditions.
