MESOFORMULA

Neuropeptides

Neuropeptides are a large group of short peptides that act as neurotransmitters or neuromodulators in the nervous system. Classical examples include endorphins and enkephalins (5 amino acids), Substance P (11 amino acids), oxytocin (9 amino acids), vasopressin (9 amino acids), and dozens of others. They are synthesized by neurons and secreted into the synaptic cleft or into the blood, binding to specific receptors on target cells. Neuropeptides regulate pain signaling, appetite, behavior, emotional responses, circadian rhythms, etc. Most neuropeptides act through membrane receptors (usually GPCRs), which trigger intracellular cascades (e.g., via cAMP, Ca²⁺), ultimately influencing gene expression in the neuron.

In the context of peptide programming, neuropeptides of interest are those that protect nerve cells and restore their functions after damage. For example, fragments of ACTH (adrenocorticotropic hormone) exhibit pronounced neurotrophic effects. In experiments on cerebral ischemia, it was shown that MEHFPGP and the related tripeptide PGP (Pro-Gly-Pro) have neuroprotective properties, stimulating angiogenesis in the damaged brain.

Specifically, these peptides increased the expression of vascular endothelial growth factor genes – VEGF-A, -B, -C, -D – and placental growth factor PlGF, promoting neovascularization in ischemic tissue. In addition, they enhanced expression of neurotrophins NGF and BDNF in various brain regions, and modulated the activity of stress-activated kinases JNK and ERK, associated with neurodegeneration. Neuropeptides increased expression of neurotrophic factors and their receptors (TrkA, TrkB, etc.) in cortex and hippocampus during ischemia. These data confirm that neuropeptides not only instantly modulate neuronal activity but also alter gene programs responsible for neuron survival and regeneration.

It is also worth mentioning neuroendocrine peptides of the hypothalamus and pituitary gland (releasing hormones: TRH – thyrotropin-releasing hormone, GnRH – gonadotropin-releasing hormone, etc.). They are very short and serve as key informational molecules linking the nervous and endocrine systems. TRH, for example, regulates thyroid activity via the pituitary gland, but also exhibits neuromodulatory properties in the CNS (antidepressant effect). Interestingly, excess or deficiency of such neuropeptides leads to pathologies: for example, hypothalamic peptide imbalance may contribute to obesity, depression, etc., by affecting gene expression in neurosecretory cells.

Modern research continues to discover new neuropeptide mediators (over 100 known peptides in the brain). They confirm that neuropeptides form a complex information network complementing classical neurotransmission. Neuropeptide regulation is characterized by duration and breadth of effect: once released, peptides can diffuse and influence many cells, setting long-term neuronal programs (lasting hours or days). This fits well with the concept of peptides as informational molecules – “slow conductors” of systemic commands to reprogram neural networks. Neuropeptides demonstrate how short signaling sequences can program brain cell activity and, potentially, be applied clinically.