Being spiritually unclean pollutes blood. Yes, it's called, in scientific terms, the either negative or positive electric charge of so called neuropeptides present in the blood, that carry it to the brain. The new brain cells that are being created by the body will be either turned to receive negative or positive neuropeptides, thus making that person being addicted to either positive free of stress state or the opposite of it. Change your mind and you will change your world. True that.
Wikipedia: "Neuropeptides are chemical messengers made up of small chains of amino acids that are synthesized and released by neurons. Neuropeptides typically bind to G protein-coupled receptors (GPCRs) to modulate neural activity and other tissues like the gut, muscles, and heart.
There are over 100 known neuropeptides, representing the largest and most diverse class of signaling molecules in the nervous system. Neuropeptides are synthesized from large precursor proteins which are cleaved and post-translationally processed then packaged into dense core vesicles. Neuropeptides are often co-released with other neuropeptides and neurotransmitters in a single neuron, yielding a multitude of effects. Once released, neuropeptides can diffuse widely to affect a broad range of targets."
Good article about neuropeptides:
https://www.mdpi.com/1422-0067/22/7/3658/htm
Abstract
The regulation of infection and inflammation by a variety of host peptides may represent an evolutionary failsafe in terms of functional degeneracy and it emphasizes the significance of host defense in survival. Neuropeptides have been demonstrated to have similar antimicrobial activities to conventional antimicrobial peptides with broad-spectrum action against a variety of microorganisms. Neuropeptides display indirect anti-infective capacity via enhancement of the host’s innate and adaptive immune defense mechanisms. However, more recently concerns have been raised that some neuropeptides may have the potential to augment microbial virulence. In this review we discuss the dual role of neuropeptides, perceived as a double-edged sword, with antimicrobial activity against bacteria, fungi, and protozoa but also capable of enhancing virulence and pathogenicity. We review the different ways by which neuropeptides modulate crucial stages of microbial pathogenesis such as adhesion, biofilm formation, invasion, intracellular lifestyle, dissemination, etc., including their anti-infective properties but also detrimental effects. Finally, we provide an overview of the efficacy and therapeutic potential of neuropeptides in murine models of infectious diseases and outline the intrinsic host factors as well as factors related to pathogen adaptation that may influence efficacy.
Keywords: neuropeptides; bacterial infections; fungal infections; protozoan infections; defense; pathogenesis; virulence; adhesion; invasion; antimicrobial activity
- Introduction
Neuropeptides are a large group of peptides that play a key role in the dialogue between the central nervous system (CNS), peripheral nervous system (PNS), and the immune system. Thus, they can be perceived not only as neurotransmitters but also as hormones or effector compounds that interact with the immune system. Neuropeptides are found in Homo sapiens and almost all animal phyla. Since the first discovery of Substance P (SP) by von Euler and Gaddum in 1931, approximately 100 different human neuropeptides and more than 80 genes encoding for neuropeptides in the H. sapiens genome have been described [1,2]. Neuropeptides are generally described as macromolecular peptides that contain between 3 and 100 amino acids in their active forms and act via G protein-coupled receptors (GPCR) [3,4,5]. It is acknowledged that neuropeptides have characteristics that are common to peptides, including post translational processing, which may influence their biological activity. Furthermore, depending on receptor expression, they can trigger cell activation at multiple locations, which in the case of neuropeptides may involve both CNS and PNS sites [2,6,7]. Neuropeptides are primarily synthesized in neuronal and glial cells [4,8]. Nevertheless, some neuropeptides are produced by non-neuronal cells, including cells of the immune system. Immune cells such as B- and T-lymphocytes, monocytes, macrophages, dendritic and mast cells as well as polymorphonuclear leukocytes have all been reported to produce these macromolecules [9,10,11]. Fibroblasts have also been shown to synthesize selected neuropeptides and neuropeptide receptors [12,13]. Since immune cells participate in a bidirectional conversation with the nervous system and other stromal cells, they act not only as producers of neuropeptides but also detect neuropeptides by neuropeptide-specific GPCRs, or by mannose receptors via a so-called “non-specific” receptor mechanism. Likewise, receptor-independent cellular activation is also possible [11,14]. Considering the interaction of neuropeptides with their specific GPCR receptors, most neuropeptides can induce modulatory actions in the cell cytoplasm via GPCR-linked pathways. The quantity of neuropeptide that is required to trigger such action is significantly lower than required for other neuro-signaling molecules [4,15]. This is perhaps related to the affinity and bond strength between the neuropeptide and the GPCR, which appears to be enhanced compared with the classical neurotransmitter-receptor linkage. In addition to their interaction with their cognate receptors, neuropeptides have also been reported to trigger ionotropic reactions [16].
Beyond the traditional role of neuropeptides as neurotransmitters in the central and peripheral neural systems, they have also antimicrobial activity contributing to the formation of local barriers of defense against a variety of pathogens. However, recent data also indicate that neuropeptides can contribute to modulating vulnerability to infection. Thus, in addition to their anti-infective action, some neuropeptides may have a completely different, unfavorable role to play in augmenting bacterial virulence. In this review, we will summarize current data on the dual modulatory role of neuropeptides in infectious diseases caused by bacteria, fungi, and protozoan parasites, including their impact on virulence, pathogenesis, and possibility of resistance development. We also critically discuss attempts to date to employ neuropeptides in animal models of infections, together with future perspectives for these important molecules. This review mainly focuses on the following neuropeptides: substance P (SP), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), pituitary andenylate cyclase-activating polypetide (PACAP), adrenomedullin (ADM), and somatostatin (SST). We also discuss the peptide hormones such as α-melanocyte stimulating hormone (α-MSH), atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP), and corticotropin-releasing hormone (CRH) as well as dynorphin as examples of opioid peptides.
- Neuropeptides as Direct and Indirect Anti-Microbial Factors
The antimicrobial properties of human neuropeptides such as SP, NPY, CGRP, VIP, ADM, and α-MSH against a variety of microorganisms are widely documented. Their direct antimicrobial activities have been confirmed to date against Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis, Aeromonas caviae) and Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans, Nocardia brasiliensis), fungi (Candida albicans, Candida tropicalis, Candida krusei, Candidia utilis, Cryptococcus neoformans, Arthroderma simii), and protozoan parasites (Trypanosoma brucei, Leishmania major) [11,17,18]. Interestingly, some highly proteolytic oral anaerobic bacteria such as Porphyromonas gingivalis and Prevotella spp have been reported to be resistant to the direct action of CGRP and ADM [19,20]. The direct action of neuropeptides encompasses both microbicidal and anti-virulent effects. The microbicidal action of neuropeptides is generally attributed to targeting the microbial membrane and causing either discrete pore formation or more extensive detergent-like disruption of the membrane. In either case, the effect is rapid, with leakage of microbial cytoplasmic contents, leading to cell death within minutes [21]. Less common, non-membrane-disruptive mechanisms of direct activity and killing have also been reported, including (i) Abnormal septum formation (scaffolding for peptidoglycan) during cell division by S. aureus in the presence of ADM [22] and (ii) ADM- and VIP-mediated disruption of intracellular endosome-lysosomal vesicles, resulting in metabolic failure in T. brucei [23]. Of note, the anti-virulent action of neuropeptides may be exemplified by the anti-proliferative (bacteriostatic) activity of somatostatin against H. pylori [24].
Considering membrane-disruptive mechanisms, an advantage of neuropeptides, like other AMPs, is their efficacy against both metabolically active and metabolically repressed microbial cells. Conversely, their significant drawback is generally rather weak microbicidal effects at physiological doses. Readers are referred to previous reviews by Augustyniak et al. and Sanz et al. [11,25] for deeper insights into the mechanisms of direct antimicrobial activities of neuropeptides.
However, in addition to direct action, neuropeptides may also display antimicrobial activity via indirect immunomodulatory effects on the innate and adaptive immune systems during the course of infection [6,26]. This humoral and cell-mediated immune modulation may be either stimulatory or inhibitory, implicating that neuropeptides have a dual role. For immunomodulating purposes, neuropeptides exploit specific receptors and also, paradoxically, utilize alternative non-cognate receptors or non-receptor-mediated mechanisms. During certain receptor–neuropeptide interactions, dual biological effects, such as for example stimulation versus inhibition of critical phagocytic events have previously been documented [11]. The stimulating potential of neuropeptides is essentially based on the intensification of mechanisms of innate defense. Modulation of critical phagocytic or mast cell function as well as triggering of proinflammatory mediators is worth mentioning in this context [6,27,28]. Conversely, a common example of inhibitory action is neuropeptide-mediated inhibition of pathogen-induced inflammation or reducing endotoxin-induced inflammatory responses. For more comprehensive information on these, we refer the reader to the previous reports [10,21,29].
It is important to note that the direct and indirect antimicrobial activities of neuropeptides presented above, are derived from in vitro studies, conducted under strictly controlled laboratory conditions, and therefore may not necessarily reflect the in vivo efficacy of the neuropeptides.
- Neuropeptides as Direct Potentiators or Amplifiers of Microbial Virulence
Virulence is defined as the ability of a pathogen to cause disease. Virulence factors are secretory, membrane-associated, or cytosolic molecules produced by bacteria, fungi, and protozoa that enable them to colonize the host at a cellular level. These factors include, among others, adhesins, toxins, enzymes, as well as factors involved in biofilm formation. Despite the role of neuropeptides in the host’s intricate defense mechanisms to control microbial invasion [11,25], these pleiotropic peptides may under certain circumstances be considered to have virulence-enhancing features [30]. The potential virulence-enhancing roles of neuropeptides can be summarized by their ability to (1) increase microbial growth; (2) increase thickness and density of microbial biofilm; (3) increase exotoxin production or bacterial cytotoxicity; (4) interfere with quorum-sensing that may control expression of virulence factors. Previous reports demonstrating the detrimental effects of neuropeptides on virulence traits are summarized in Table 1 and Figure 1 and discussed in further detail below.
https://www.mdpi.com/1422-0067/22/7/3658/htm
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