Concepts for Biologically Active Peptides

Abstract

Here we review a unique aspect of CNS research on biologically active peptides that started against a background of prevalent dogmas but ended by exerting considerable influence on the field. During the course of refuting some doctrines, we introduced several concepts that were unconventional and paradigm-shifting at the time. We showed that (1) hypothalamic peptides can act ‘up’ on the brain as well as ‘down’ on the pituitary, (2) peripheral peptides can affect the brain, (3) peptides can cross the blood-brain barrier, (4) the actions of peptides can persist longer than their half-lives in blood, (5) perinatal administration of peptides can exert actions persisting into adulthood, (6) a single peptide can have more than one action, (7) dose-response relationships of peptides need not be linear, (8) the brain produces antiopiate as well as opiate peptides, (9) there is a selective high affinity endogenous peptide ligand for the mu-opiate receptor, (10) a peptide’s name does not restrict its effects, and (11) astrocytes assume an active role in response to metabolic disturbance and hyperleptinemia. The evolving questions in our laboratories reflect the diligent effort of the neuropeptide community to identify the roles of peptides in the CNS. The next decade is expected to see greater progress in the following areas: (a) interactions of peptides with other molecules in the CNS; (b) peptide involvement in cell-cell interactions; and (c) peptides in neuropsychiatric, autoimmune, and neurodegenerative diseases. The development of peptidomics and gene silencing approaches will expedite the formation of many new concepts in a new era.

The “psychomicrobiotic”: Targeting microbiota in major psychiatric disorders: A systematic review

“…Leakage of LPS from the intestine might be a trigger for peripheral inflammatory responses that lead to de novo production of cytokines in the brain. Improving the epithelial barrier may reduce traffic of bacteria and their byproducts and hence be a way to stop the inflammatory response; neuropeptides synthesis (for a review see [18]); modulation of local and peripheral inflammation. The gut microbiota regulates the development of lymphoid structures and modulates the differentiation of immune cell subsets thus maintaining homeostatic interactions between the host and the gut microbiota (for review see [19]).…”

Relaxin-3 systems in the brain—The first 10 years

“…Although not their primary function, arousal systems are also able to modulate feeding/metabolism and stress responses. As a growing number of experimental studies support the theory that relaxin-3 can act as an arousal transmitter, it is our view that subsequent functional reports should describe their findings on relaxin-3 in terms of a more integrated theory of relaxin-3 function (see also Kastin and Pan, 2010).…”

Endocrine approaches to treatment of Alzheimer's disease and other neurological conditions

“…There was also the issue of our clear leadership in the chemical, physiological and clinical advances on LH-RH [26,43,[47][48][49][50][51]72,90,93]. Dr. Kastin's work on MIF and MSH established his leading position in the fields of both MSH and MIF, as he was the first to show that a hypothalamic peptide could act "upward" on the brain, as we had previously shown for hypothalamic peptides acting "downward" on the pituitary [40][41][42]45,46].…”

“…As a result of realizing that peptides could act "upward" on the brain, Dr. Kastin became very interested in the behavioral and CNS effects of hypothalamic hormones and related compounds such as endorphins and enkephalins and so he started elaborate studies on the influence of our synthetic TRH, LHRH, somatostatin, and their analogs, on the brain [46]. As mentioned above his work with MSH was the first to show that any peripherally generated peptide could have direct effects on the brain.…”

“…Various studies have demonstrated that some hypothalamic neurohormone analogs can affect CNS functions [20,[36][37][38][39][40][41][42][44][45][46]62,63,84,85,91]. Thus, these studies suggest that neuroendocrine mechanisms could play a contributive role in the development of AD.…”