NFKF is a synthetic fragment derived from rat hemopressin that protects mice from neurodegeneration

Heimann, Andrea S.; Giardini, Aline Carolina; Sant’Anna, Morena Brazil; Santos, Nilton Barreto dos; Gewehr, Mayara C.F.; Munhoz, Carolina Demarchi; Castro, Leandro M.; Picolo, Gisele; Remer, Ricardo A.; Ferro, Emer S.

doi:10.1016/j.neulet.2020.134765

Cited by 9 publications

(7 citation statements)

References 35 publications

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“…Recently, animal and cell culture models have been used to reveal the function of peptides in different systems of the body, whether neuropeptides, which are better studied 45 or so-called intracellular peptides, derived from intracellular proteins. 30,46,47 The main changes observed in the present report after treatment with 6-OHDA were in the relative levels of peptides derived from intracellular proteins. These data suggest for the first time that intracellular peptides have biological significance in PD.…”

Section: Discussionmentioning

confidence: 47%

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Peptide Profile of Zebrafish Brain in a 6-OHDA-Induced Parkinson Model

2021

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Parkinson's disease (PD) is a chronic neurodegenerative disorder mainly attributed to the progressive loss of dopaminergic neurons in the substantia nigra, which leads to uncontrolled voluntary movements causing tremors, postural instability, joint stiffness, and speech and locomotion difficulties, among other symptoms. Previous studies have shown the participation of specific peptides in neurodegenerative diseases. In this context, the present work analyzed changes in the peptide profile in zebrafish brain induced to parkinsonian conditions with 6-hydroxydopamine, using isotopic labeling techniques plus mass spectrometry. These analyses allowed the relative quantitation and identification of 118 peptides. Of these, nine peptides showed significant changes, one peptide was increased and eight decreased. The most altered sequences were fragment of cytosolic and extracellular proteins related to lipid metabolism and dynamic cytoskeleton. These results open new perspectives of study about the function of peptides in PD.

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Section: Discussionmentioning

confidence: 47%

“…29 Intracellular peptides have been extensively shown to have both biological and pharmacological activities. 30,31 Animal models have been used to mimic PD by natural or synthetic neurotoxins or with in vivo mutations. 32,33 PD can be induced by injecting 6-OHDA into small vertebrate fish such as zebrafish (Danio rerio).…”

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confidence: 99%

Peptide Profile of Zebrafish Brain in a 6-OHDA-Induced Parkinson Model

2021

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“…In an experimental autoimmune encephalomyelitis model of multiple sclerosis, the oral administration of rat hemopressin fragment NFKF improved clinical scores and locomotor activity. Interestingly, NFKF blocked the production of IL-1β and IL-6 in spleen leukocytes possibly via CB2 receptor activation, while in the inguinal lymph nodes only IL-1ß was significantly reduced, suggesting a role for these peptides in the treatment of multiple sclerosis (Heimann et al, 2020). However, effects within the CNS must be considered, since Xapelli et al (2014) showed hemopressin increased oligodendrocyte differentiation of subventricular zone progenitor cells in vitro (Xapelli et al, 2014).…”

Section: Hemopressin Peptides In Physiological Functionsmentioning

confidence: 99%

“…However, RVD-Hp did not influence CP55,940induced β-arrestin2 recruitment. Recently, there are other peptide endocannabinoids suggested to have an allosteric modulation of CB1/CB2 receptors such as NFKF (Heimann et al, 2020).…”

Section: Modulation Of Cannabinoid Receptors By Peptide Cannabinoidsmentioning

confidence: 99%

New Insights Into Peptide Cannabinoids: Structure, Biosynthesis and Signaling

et al. 2020

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Classically, the endocannabinoid system (ECS) consists of endogenous lipids, of which the best known are anandamide (AEA) and 2 arachidonoylglycerol (2-AG), their enzyme machinery for synthesis and degradation and their specific receptors, cannabinoid receptor one (CB1) and cannabinoid receptor two (CB2). However, endocannabinoids also bind to other groups of receptors. Furthermore, another group of lipids are considered to be endocannabinoids, such as the fatty acid ethanolamides, the fatty acid primary amides and the monoacylglycerol related molecules. Recently, it has been shown that the hemopressin peptide family, derived from α and β chains of hemoglobins, is a new family of cannabinoids. Some studies indicate that hemopressin peptides are expressed in the central nervous system and peripheral tissues and act as ligands of these receptors, thus suggesting that they play a physiological role. In this review, we examine new evidence on lipid endocannabinoids, cannabinoid receptors and the modulation of their signaling pathways. We focus our discussion on the current knowledge of the pharmacological effects, the biosynthesis of the peptide cannabinoids and the new insights on the activation and modulation of cannabinoid receptors by these peptides. The novel peptide compounds derived from hemoglobin chains and their non-classical activation of cannabinoid receptors are only starting to be uncovered. It will be exciting to follow the ensuing discoveries, not only in reference to what is already known of the classical lipid endocannabinoids revealing more complex aspects of endocannabinoid system, but also as to its possibilities as a future therapeutic tool.

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“…HP extended forms (RVDand VD-HP) are agonists of CB1 receptors (Gomes et al, 2009). An HP fragment NFKF was recently shown to promote analgesia, delay seizure induced by pilocarpine, and prevent neurodegeneration in an experimental model of autoimmune encephalomyelitis (Heimann et al, 2020b). These effects have caught the attention of pharmaceutical companies.…”

Section: What Does the Endocannabinoid System Consist Of?mentioning

confidence: 99%

Quality of Life and a Surveillant Endocannabinoid System

et al. 2021

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The endocannabinoid system (ECS) is an important brain modulatory network. ECS regulates brain homeostasis throughout development, from progenitor fate decision to neuro- and gliogenesis, synaptogenesis, brain plasticity and circuit repair, up to learning, memory, fear, protection, and death. It is a major player in the hypothalamic-peripheral system-adipose tissue in the regulation of food intake, energy storage, nutritional status, and adipose tissue mass, consequently affecting obesity. Loss of ECS control might affect mood disorders (anxiety, hyperactivity, psychosis, and depression), lead to drug abuse, and impact neurodegenerative (Alzheimer’s, Parkinson, Huntington, Multiple, and Amyotrophic Lateral Sclerosis) and neurodevelopmental (autism spectrum) disorders. Practice of regular physical and/or mind-body mindfulness and meditative activities have been shown to modulate endocannabinoid (eCB) levels, in addition to other players as brain-derived neurotrophic factor (BDNF). ECS is involved in pain, inflammation, metabolic and cardiovascular dysfunctions, general immune responses (asthma, allergy, and arthritis) and tumor expansion, both/either in the brain and/or in the periphery. The reason for such a vast impact is the fact that arachidonic acid, a precursor of eCBs, is present in every membrane cell of the body and on demand eCBs synthesis is regulated by electrical activity and calcium shifts. Novel lipid (lipoxins and resolvins) or peptide (hemopressin) players of the ECS also operate as regulators of physiological allostasis. Indeed, the presence of cannabinoid receptors in intracellular organelles as mitochondria or lysosomes, or in nuclear targets as PPARγ might impact energy consumption, metabolism and cell death. To live a better life implies in a vigilant ECS, through healthy diet selection (based on a balanced omega-3 and -6 polyunsaturated fatty acids), weekly exercises and meditation therapy, all of which regulating eCBs levels, surrounded by a constructive social network. Cannabidiol, a diet supplement has been a major player with anti-inflammatory, anxiolytic, antidepressant, and antioxidant activities. Cognitive challenges and emotional intelligence might strengthen the ECS, which is built on a variety of synapses that modify human behavior. As therapeutically concerned, the ECS is essential for maintaining homeostasis and cannabinoids are promising tools to control innumerous targets.

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NFKF is a synthetic fragment derived from rat hemopressin that protects mice from neurodegeneration

Cited by 9 publications

References 35 publications

Peptide Profile of Zebrafish Brain in a 6-OHDA-Induced Parkinson Model

Peptide Profile of Zebrafish Brain in a 6-OHDA-Induced Parkinson Model

New Insights Into Peptide Cannabinoids: Structure, Biosynthesis and Signaling

Quality of Life and a Surveillant Endocannabinoid System

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