What are neuropeptides?

We know neuropeptides now for over 40 years as chemical signals in the brain. The discovery of neuropeptides is founded on groundbreaking research in physiology, endocrinology, and biochemistry during the last century and has been built on three seminal notions: (1) peptide hormones are chemical signals in the endocrine system; (2) neurosecretion of peptides is a general principle in the nervous system; and (3) the nervous system is responsive to peptide signals. These historical lines have contributed to how neuropeptides can be defined today: "Neuropeptides are small proteinaceous substances produced and released by neurons through the regulated secretory route and acting on neural substrates." Thus, neuropeptides are the most diverse class of signaling molecules in the brain engaged in many physiological functions. According to this definition almost 70 genes can be distinguished in the mammalian genome, encoding neuropeptide precursors and a multitude of bioactive neuropeptides. In addition, among cytokines, peptide hormones, and growth factors there are several subfamilies of peptides displaying most of the hallmarks of neuropeptides, for example neural chemokines, cerebellins, neurexophilins, and granins. All classical neuropeptides as well as putative neuropeptides from the latter families are presented as a resource.