Neuropeptide Y: A stressful review

Stress is defined as an adverse condition that disturbs the homeostasis of the body and activates adaptation responses. Among the many pathways and mediators involved, neuropeptide Y (NPY) stands out due to its unique stress-relieving, anxiolytic and neuroprotective properties. Stress exposure alters the biosynthesis of NPY in distinct brain regions, the magnitude and direction of this effect varying with the duration and type of stress. NPY is expressed in particular neurons of the brainstem, hypothalamus and limbic system, which explains why NPY has an impact on stress-related changes in emotional-affective behaviour and feeding as well as on stress coping. The biological actions of NPY in mammals are mediated by the Y1, Y2, Y4 and Y5 receptors, Y1 receptor stimulation being anxiolytic whereas Y2 receptor activation is anxiogenic. Emerging evidence attributes NPY a role in stress resilience, the ability to cope with stress. Thus there is a negative correlation between stress-induced behavioural disruption and cerebral NPY expression in animal models of post-traumatic stress disorder. Exogenous NPY prevents the negative consequences of stress, and polymorphisms of the NPY gene are predictive of impaired stress processing and increased risk of neuropsychiatric diseases. Stress is also a factor contributing to, and resulting from, neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's disease, in which NPY appears to play an important neuroprotective role. This review summarizes the evidence for an implication of NPY in stress-related and neurodegenerative pathologies and addresses the cerebral NPY system as a therapeutic target.