Cyclic Peptides in Neurological Disorders: The Case of Cyclo(His-Pro)

Communication between and within communities of cells or independent organisms is a crucial prerequisite for species survival. In response to variations in the extracellular environment, the collective behavior of cell populations can be coordinated by regulating community-level gene expression. This mechanism is strongly conserved during evolution, being shared both by bacterial communities and central nervous system cells. Notably, cyclic dipeptides (CDPs) are molecules that are implicated in these quorum sensing behaviors in both settings. Bacteria coordinate their collective behavior by producing CDPs (quorum sensing inducers) that enhance the capacity of individual members of the community to detect these signals and thus amplify the community-level response. In this review, we highlight recent data indicating that strikingly similar molecular mechanisms control communications between glial and neuronal cells to maintain homeostasis in the central nervous system, with a specific focus on the role of the thyrotropin-releasing hormone—derived CDP cyclo(His-Pro) in the protection against neurotoxic insults.