Natriuretic peptides (NPs) are traditionally known as cardiac hormones with diuretic, natriuretic and blood pressure lowering properties. Evidence indicates that NPs and their receptors are abundant in the central nervous system, suggesting their involvement in regulation of various brain functions. It has been shown that NPs are involved in the regulation of neurovascular and blood-brain barrier integrity, neuro-inflammation, neuroprotection, synaptic transmission and brain fluid homeostasis. In addition, NPs might contribute to the brain’s inhibitory control over the hypothalamic-pituitary-adrenal axis. Studies have also shown that high systemic levels of NPs are associated with cognitive impairment independent of cardiovascular risk factors. In this review we discuss the potential roles of NPs in regulating structural and functional integrity of the brain. Based on the available neurobiological and clinical evidence, we propose that NPs might represent as potential novel diagnostic and therapeutic targets for cognitive impairment.

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