Direct and Indirect Antimicrobial Activities of Neuropeptides and their Therapeutic Potential

Abstract

As global resistance to conventional antibiotics rises we need to develop new strategies to develop future novel therapeutics. In our quest to design novel anti-infectives and antimicrobials it is of interest to investigate host-pathogen interactions and learn from the complexity of host defense strategies that have evolved over millennia. A myriad of host defense molecules are now known to play a role in protection against human infection. However, the interaction between host and pathogen is recognized to be a multifaceted one, involving countless host proteins, including several families of peptides. The regulation of infection and inflammation by multiple peptide families may represent an evolutionary failsafe in terms of functional degeneracy and emphasizes the significance of host defense in survival. One such family is the neuropeptides (NPs), which are conventionally defined as peptide neurotransmitters but have recently been shown to be pleiotropic molecules that are integral components of the nervous and immune systems. In this review we address the antimicrobial and anti-infective effects of NPs both in vitro and in vivo and discuss their potential therapeutic usefulness in overcoming infectious diseases. With improved understanding of the efficacy of NPs, these molecules could become an important part of our arsenal of weapons in the treatment of infection and inflammation. It is envisaged that targeted therapy approaches that selectively exploit the anti-infective, antimicrobial and immunomodulatory properties of NPs could become useful adjuncts to our current therapeutic modalities.

Therapeutic Efficacy of Stable Analogues of Vasoactive Intestinal Peptide against Pathogens

“…These molecules, termed host defense peptides, have emerged as potential therapeutic candidates. Recently, some neuropeptides, which are pleiotropic and integral components of the neuroendocrine system, have been recognized as host defense peptides (3).…”

Dynamic Role of Host Stress Responses in Modulating the Cutaneous Microbiome: Implications for Wound Healing and Infection

“…20,34 Induces keratinocytes to express endogenous AMPs through a TLR2-dependent mechanism. 20,34 S. aureus Induction of hBD3 gene expression is TLR2 dependent.…”

“…20,34 Induces keratinocytes to express endogenous AMPs through a TLR2-dependent mechanism. 20,34 S. aureus Induction of hBD3 gene expression is TLR2 dependent. 20,34 Bacterial lipoproteins and lipoteichoic acid serve as TLR2/6 or TLR2/2 agonists.…”

“…20,34 S. aureus Induction of hBD3 gene expression is TLR2 dependent. 20,34 Bacterial lipoproteins and lipoteichoic acid serve as TLR2/6 or TLR2/2 agonists. 53 …”

“…; Table 3) 33,34 with the capacity to suppress or enhance innate immune responses [reviewed in Radek 18 ]. This data indicates that the skin microbiome must be regulated by dermatotopography, as well as the concentration and activity of neuropeptides and endogenous stress hormones secreted by resident cells of the epidermis and dermis during stress.…”