Biomolecular Concepts[JOURNAL]
Sun
200 papers
The evolving world of ubiquitin: transformed polyubiquitin chains.
Morimoto D, Shirakawa M
Biomol Concepts · 2016 Jun · PMID 27226101 · Publisher ↗
The regulation of diverse cellular events by proteins that have undergone post-translational modification with ubiquitin is well documented. Ubiquitin can be polymerized and eight types of polyubiquitin chain contribute...
The regulation of diverse cellular events by proteins that have undergone post-translational modification with ubiquitin is well documented. Ubiquitin can be polymerized and eight types of polyubiquitin chain contribute to the complexity and specificity of the ubiquitin signal. Unexpectedly, recent studies have shown that ubiquitin itself undergoes post-translational modification by acetylation and phosphorylation; moreover, amyloid-like fibrils comprised of polyubiquitin chains have been discovered. Thus, ubiquitin is not only conjugated to substrate proteins, but also modified and transformed itself. Here, we review these novel forms of ubiquitin signal, with a focus on fibril formation of polyubiquitin chains and its underlying biological relevance.
Recent advances in the characterization of Crl, the unconventional activator of the stress sigma factor σS/RpoS.
Cavaliere P, Norel F
Biomol Concepts · 2016 Jun · PMID 27180360 · Publisher ↗
The bacterial RNA polymerase (RNAP) holoenzyme is a multisubunit core enzyme associated with a σ factor that is required for promoter-specific transcription initiation. Besides a primary σ responsible for most of the gen...
The bacterial RNA polymerase (RNAP) holoenzyme is a multisubunit core enzyme associated with a σ factor that is required for promoter-specific transcription initiation. Besides a primary σ responsible for most of the gene expression during active growth, bacteria contain alternative σ factors that control adaptive responses. A recurring strategy in the control of σ factor activity is their sequestration by anti-sigma factors that occlude the RNAP binding determinants, reducing their activity. In contrast, the unconventional transcription factor Crl binds specifically to the alternative σ factor σS/RpoS, and favors its association with the core RNAP, thereby increasing its activity. σS is the master regulator of the general stress response that protects many Gram-negative bacteria from several harmful environmental conditions. It is also required for biofilm formation and virulence of Salmonella enterica serovar Typhimurium. In this report, we discuss current knowledge on the regulation and function of Crl in Salmonella and Escherichia coli, two bacterial species in which Crl has been studied. We review recent advances in the structural characterization of the Crl-σS interaction that have led to a better understanding of this unusual mechanism of σ regulation.
The clear and dark sides of water: influence on the coiled coil folding domain.
Vajda T, Perczel A
Biomol Concepts · 2016 Jun · PMID 27180359 · Publisher ↗
The essential role of water in extra- and intracellular coiled coil structures of proteins is critically evaluated, and the different protein types incorporating coiled coil units are overviewed. The following subjects a...
The essential role of water in extra- and intracellular coiled coil structures of proteins is critically evaluated, and the different protein types incorporating coiled coil units are overviewed. The following subjects are discussed: i) influence of water on the formation and degradation of the coiled coil domain together with the stability of this conformer type; ii) the water's paradox iii) design of coiled coil motifs and iv) expert opinion and outlook is presented. The clear and dark sides refer to the positive and negative aspects of the water molecule, as it may enhance or inhibit a given folding event. This duplicity can be symbolized by the Roman 'Janus-face' which means that water may facilitate and stimulate coiled coil structure formation, however, it may contribute to the fatal processes of oligomerization and amyloidosis of the very same polypeptide chain.
Inspiration from the mirror: D-amino acid containing peptides in biomedical approaches.
Feng Z, Xu B
Biomol Concepts · 2016 Jun · PMID 27159920 · Full text
D-amino acids, the enantiomers of naturally abundant L-amino acids, bear unique stereochemistry properties that lead to the resistance towards most of the endogenous enzymes. Previous works have demonstrated applications...
D-amino acids, the enantiomers of naturally abundant L-amino acids, bear unique stereochemistry properties that lead to the resistance towards most of the endogenous enzymes. Previous works have demonstrated applications of D-amino acids in therapeutic development with the aid of mirror-image phage display and retro-inverso peptide synthesis. In this review, we highlight the recent progress and challenges in the exploration of D-amino acids at the interface of chemistry and life science. First, we will introduce some progress made in traditional application of D-amino acids to enhance biostability of peptide therapeutics. Then, we discuss some works that explore the relatively underexplored interactions between the enzyme and D-amino acids and enzymatic reactions of D-amino acids. To highlight the enzymatic reactions of D-amino acids, we will describe several emerging works on the enzyme-instructed self-assembly (EISA) and their potential application in selective anti-inflammatory or anticancer therapies. At the end, we briefly mention the challenges and possible future directions.
Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation.
Viloria K, Hill NJ
Biomol Concepts · 2016 May · PMID 27135623 · Publisher ↗
Matricellular proteins influence wide-ranging fundamental cellular processes including cell adhesion, migration, growth and differentiation. They achieve this both through interactions with cell surface receptors and reg...
Matricellular proteins influence wide-ranging fundamental cellular processes including cell adhesion, migration, growth and differentiation. They achieve this both through interactions with cell surface receptors and regulation of the matrix environment. Many matricellular proteins are also associated with diverse clinical disorders including cancer and diabetes. Alternative splicing is a precisely regulated process that can produce multiple isoforms with variable functions from a single gene. To date, the expression of alternate transcripts for the matricellular family has been reported for only a handful of genes. Here we analyse the evidence for alternative splicing across the matricellular family including the secreted protein acidic and rich in cysteine (SPARC), thrombospondin, tenascin and CCN families. We find that matricellular proteins have double the average number of splice variants per gene, and discuss the types of domain affected by splicing in matricellular proteins. We also review the clinical significance of alternative splicing for three specific matricellular proteins that have been relatively well characterised: osteopontin (OPN), tenascin-C (TNC) and periostin. Embracing the complexity of matricellular splice variants will be important for understanding the sometimes contradictory function of these powerful regulatory proteins, and for their effective clinical application as biomarkers and therapeutic targets.
Immunoproteomics technologies in the discovery of autoantigens in autoimmune diseases.
Ganesan V, Ascherman DP, Minden JS
Biomol Concepts · 2016 May · PMID 27115324 · Publisher ↗
Proteomics technologies are often used for the identification of protein targets of the immune system. Here, we discuss the immunoproteomics technologies used for the discovery of autoantigens in autoimmune diseases wher...
Proteomics technologies are often used for the identification of protein targets of the immune system. Here, we discuss the immunoproteomics technologies used for the discovery of autoantigens in autoimmune diseases where immune system dysregulation plays a central role in disease onset and progression. These autoantigens and associated autoantibodies can be used as potential biomarkers for disease diagnostics, prognostics and predicting/monitoring drug responsiveness (theranostics). Here, we compare a variety of methods such as mass spectrometry (MS)-based [serological proteome analysis (SERPA), antibody mediated identification of antigens (AMIDA), circulating immune complexome (CIC) analysis, surface enhanced laser desorption/ionization-time of flight (SELDI-TOF)], nucleic acid based serological analysis of antigens by recombinant cDNA expression cloning (SEREX), phage immunoprecipitation sequencing (PhIP-seq) and array-based immunoscreening (proteomic microarrays), luciferase immunoprecipitation systems (LIPS), nucleic acid programmable protein array (NAPPA) methods. We also review the relevance of immunoproteomic data generated in the last 10 years, with a focus on the aforementioned MS based methods.
Histone acetylation in neuronal (dys)function.
Bonnaud EM, Suberbielle E, Malnou CE
Biomol Concepts · 2016 May · PMID 27101554 · Publisher ↗
Cognitive functions require the expression of an appropriate pattern of genes in response to environmental stimuli. Over the last years, many studies have accumulated knowledge towards the understanding of molecular mech...
Cognitive functions require the expression of an appropriate pattern of genes in response to environmental stimuli. Over the last years, many studies have accumulated knowledge towards the understanding of molecular mechanisms that regulate neuronal gene expression. Epigenetic modifications have been shown to play an important role in numerous neuronal functions, from synaptic plasticity to learning and memory. In particular, histone acetylation is a central player in these processes. In this review, we present the molecular mechanisms of histone acetylation and summarize the data underlying the relevance of histone acetylation in cognitive functions in normal and pathological conditions. In the last part, we discuss the different mechanisms underlying the dysregulation of histone acetylation associated with neurological disorders, with a particular focus on environmental causes (stress, drugs, or infectious agents) that are linked to impaired histone acetylation.
Interstitial cells of Cajal and telocytes in the gut: twins, related or simply neighbor cells?
Vannucchi MG, Traini C
Biomol Concepts · 2016 May · PMID 26992201 · Publisher ↗
In the interstitium of the connective tissue several types of cells occur. The fibroblasts, responsible for matrix formation, the mast cells, involved in local response to inflammatory stimuli, resident macrophages, plas...
In the interstitium of the connective tissue several types of cells occur. The fibroblasts, responsible for matrix formation, the mast cells, involved in local response to inflammatory stimuli, resident macrophages, plasma cells, lymphocytes, granulocytes and monocytes, all engaged in immunity responses. Recently, another type of interstitial cell, found in all organs so far examined, has been added to the previous ones, the telocytes (TC). In the gut, in addition to the cells listed above, there are also the interstitial cells of Cajal (ICC), a peculiar type of cell exclusively detected in the alimentary tract with multiple functions including pace-maker activity. The possibility that TC and ICC could correspond to a unique cell type, where the former would represent an ICC variant outside the gut, was initially considered, however, further studies have clearly shown that ICC and TC are two distinct types of cells. In the gut, while the features and the roles of the ICC are established, part of the scientific community is still disputing these 'new' interstitial cells to which several names such as fibroblast-like cells (FLCs), interstitial Cajal-like cells or, most recently, PDGFRα+ cells have been attributed. This review will detail the main features and roles of the TC and ICC with the aim to establish their relationships and hopefully define the identity of the TC in the gut.
Lessons from mammalian hibernators: molecular insights into striated muscle plasticity and remodeling.
Tessier SN, Storey KB
Biomol Concepts · 2016 May · PMID 26982616 · Publisher ↗
Striated muscle shows an amazing ability to adapt its structural apparatus based on contractile activity, loading conditions, fuel supply, or environmental factors. Studies with mammalian hibernators have identified a va...
Striated muscle shows an amazing ability to adapt its structural apparatus based on contractile activity, loading conditions, fuel supply, or environmental factors. Studies with mammalian hibernators have identified a variety of molecular pathways which are strategically regulated and allow animals to endure multiple stresses associated with the hibernating season. Of particular interest is the observation that hibernators show little skeletal muscle atrophy despite the profound metabolic rate depression and mechanical unloading that they experience during long weeks of torpor. Additionally, the cardiac muscle of hibernators must adjust to low temperature and reduced perfusion, while the strength of contraction increases in order to pump cold, viscous blood. Consequently, hibernators hold a wealth of knowledge as it pertains to understanding the natural capacity of myocytes to alter structural, contractile and metabolic properties in response to environmental stimuli. The present review outlines the molecular and biochemical mechanisms which play a role in muscular atrophy, hypertrophy, and remodeling. In this capacity, four main networks are highlighted: (1) antioxidant defenses, (2) the regulation of structural, contractile and metabolic proteins, (3) ubiquitin proteosomal machinery, and (4) macroautophagy pathways. Subsequently, we discuss the role of transcription factors nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Myocyte enhancer factor 2 (MEF2), and Forkhead box (FOXO) and their associated posttranslational modifications as it pertains to regulating each of these networks. Finally, we propose that comparing and contrasting these concepts to data collected from model organisms able to withstand dramatic changes in muscular function without injury will allow researchers to delineate physiological versus pathological responses.
Life in the cold: links between mammalian hibernation and longevity.
Wu CW, Storey KB
Biomol Concepts · 2016 Feb · PMID 26820181 · Publisher ↗
The biological process of aging is the primary determinant of lifespan, but the factors that influence the rate of aging are not yet clearly understood and remain a challenging question. Mammals are characterized by >100...
The biological process of aging is the primary determinant of lifespan, but the factors that influence the rate of aging are not yet clearly understood and remain a challenging question. Mammals are characterized by >100-fold differences in maximal lifespan, influenced by relative variances in body mass and metabolic rate. Recent discoveries have identified long-lived mammalian species that deviate from the expected longevity quotient. A commonality among many long-lived species is the capacity to undergo metabolic rate depression, effectively re-programming normal metabolism in response to extreme environmental stress and enter states of torpor or hibernation. This stress tolerant phenotype often involves a reduction in overall metabolic rate to just 1-5% of the normal basal rate as well as activation of cytoprotective responses. At the cellular level, major energy savings are achieved via coordinated suppression of many ATP-expensive cell functions; e.g. global rates of protein synthesis are strongly reduced via inhibition of the insulin signaling axis. At the same time, various studies have shown activation of stress survival signaling during hibernation including up-regulation of protein chaperones, increased antioxidant defenses, and transcriptional activation of pro-survival signaling such as the FOXO and p53 pathways. Many similarities and parallels exist between hibernation phenotypes and different long-lived models, e.g. signal transduction pathways found to be commonly regulated during hibernation are also known to induce lifespan extension in animals such as Drosophila melanogaster and Caenorhabditis elegans. In this review, we highlight some of the molecular mechanisms that promote longevity in classic aging models C. elegans, Drosophila, and mice, while providing a comparative analysis to how they are regulated during mammalian hibernation.
Physiological and pathological roles of exosomes in the nervous system.
Yuyama K, Igarashi Y
Biomol Concepts · 2016 Feb · PMID 26812803 · Publisher ↗
Exosomes represent a subtype of extracellular nanovesicles that are generated from the luminal budding of limiting endosomal membranes and subsequent exocytosis. They encapsulate or associate with obsolete molecules to e...
Exosomes represent a subtype of extracellular nanovesicles that are generated from the luminal budding of limiting endosomal membranes and subsequent exocytosis. They encapsulate or associate with obsolete molecules to eliminate or to transfer their cargos in intercellular communication. The exosomes are also released and transported between neurons and glia in the nervous system, having a broad impact on nerve development, activation and regeneration. Accumulating evidence suggests that the exosomes are attributed to the pathogenesis of several neurodegenerative diseases such as prion disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, as well as aging, in which the exosomes lack the capacity for cellular self-repair and spread their enclosed pathological agents among neurons. In this article, we review the current proposed functions of exosomes in physiological and pathological processes in the nervous system.
Extended functional repertoire for human copper chaperones.
Matson Dzebo M, Ariöz C, Wittung-Stafshede P
Biomol Concepts · 2016 Feb · PMID 26745464 · Publisher ↗
Copper (Cu) ions are cofactors in many essential enzymes. As free Cu ions are toxic, most organisms have highly specialized Cu transport systems involving dedicated proteins. The human cytoplasmic Cu chaperone Atox1 deli...
Copper (Cu) ions are cofactors in many essential enzymes. As free Cu ions are toxic, most organisms have highly specialized Cu transport systems involving dedicated proteins. The human cytoplasmic Cu chaperone Atox1 delivers Cu to P1B-type ATPases in the Golgi network, for incorporation into Cu-dependent enzymes following the secretory path. Atox1 homologs are found in most organisms; it is a 68-residue ferredoxin-fold protein that binds Cu in a conserved surface-exposed CXXC motif. In addition to Atox1, the human cytoplasm also contains Cu chaperones for loading of superoxide dismutase 1 (i.e. CCS) and cytochrome c oxidase in mitochondria (i.e. Cox17). Many mechanistic aspects have been resolved with respect to how Cu ions are moved between these proteins. In addition to the primary cytoplasmic Cu chaperone function, all three cytoplasmic chaperones have been reported to have other interaction partners that are involved in signaling pathways that modulate cell growth and development. These new discoveries imply that humans have evolved a highly sophisticated network of control mechanisms that connect Cu transport with cell regulatory processes. This knowledge may eventually be exploited for future drug developments towards diseases such as cancer and neurodegenerative disorders.
The dendritic cell side of the immunological synapse.
Verboogen DR, Dingjan I, Revelo NH … +3 more , Visser LJ, ter Beest M, van den Bogaart G
Biomol Concepts · 2016 Feb · PMID 26741354 · Publisher ↗
Immune responses are initiated by the interactions between antigen-presenting cells (APCs), such as dendritic cells (DCs), with responder cells, such as T cells, via a tight cellular contact interface called the immunolo...
Immune responses are initiated by the interactions between antigen-presenting cells (APCs), such as dendritic cells (DCs), with responder cells, such as T cells, via a tight cellular contact interface called the immunological synapse. The immunological synapse is a highly organized subcellular structure that provides a platform for the presentation of antigen in major histocompatibility class I and II complexes (MHC class I and II) on the surface of the APC to receptors on the surface of the responder cells. In T cells, these contacts lead to highly polarized membrane trafficking that results in the local release of lytic granules and in the delivery and recycling of T cell receptors at the immunological synapse. Localized trafficking also occurs at the APC side of the immunological synapse, especially in DCs where antigen loaded in MHC class I and II is presented and cytokines are released specifically at the synapse. Whereas the molecular mechanisms underlying polarized membrane trafficking at the T cell side of the immunological synapse are increasingly well understood, these are still very unclear at the APC side. In this review, we discuss the organization of the APC side of the immunological synapse. We focus on the directional trafficking and release of membrane vesicles carrying MHC molecules and cytokines at the immunological synapses of DCs. We hypothesize that the specific delivery of MHC and the release of cytokines at the immunological synapse mechanistically resemble that of lytic granule release from T cells.
The CLU-files: disentanglement of a mystery.
Rohne P, Prochnow H, Koch-Brandt C
Biomol Concepts · 2016 Feb · PMID 26673020 · Publisher ↗
The multifaceted protein clusterin (CLU) has been challenging researchers for more than 35 years. The characterization of CLU as a molecular chaperone was one of the major breakthroughs in CLU research. Today, secretory...
The multifaceted protein clusterin (CLU) has been challenging researchers for more than 35 years. The characterization of CLU as a molecular chaperone was one of the major breakthroughs in CLU research. Today, secretory clusterin (sCLU), also known as apolipoprotein J (apoJ), is considered one of the most important extracellular chaperones ever found. It is involved in a broad range of physiological and pathophysiological functions, where it exerts a cytoprotective role. Descriptions of various forms of intracellular CLU have led to further and even contradictory functions. To untangle the current state of knowledge of CLU, this review will combine old views in the field, with new discoveries to highlight the nature and function of this fascinating protein(s). In this review, we further describe the expression and subcellular location of various CLU forms. Moreover, we discuss recent insights into the structure of CLU and assess how structural properties as well as the redox environment determine the chaperone activity of CLU. Eventually, the review connects the biochemistry and molecular cell biology of CLU with medical aspects, to formulate a hypothesis of a CLU function in health and disease.
Recent advances in siRNA delivery.
Sarisozen C, Salzano G, Torchilin VP
Biomol Concepts · 2015 Dec · PMID 26609865 · Publisher ↗
In the 1990s an unexpected gene-silencing phenomena in plants, the later called RNA interference (RNAi), perplexed scientists. Following the proof of activity in mammalian cells, small interfering RNAs (siRNAs) have quic...
In the 1990s an unexpected gene-silencing phenomena in plants, the later called RNA interference (RNAi), perplexed scientists. Following the proof of activity in mammalian cells, small interfering RNAs (siRNAs) have quickly crept into biomedical research as a new powerful tool for the potential treatment of different human diseases based on altered gene expression. In the past decades, several promising data from ongoing clinical trials have been reported. However, despite surprising successes in many pre-clinical studies, concrete obstacles still need to be overcome to translate therapeutic siRNAs into clinical reality. Here, we provide an update on the recent advances of RNAi-based therapeutics and highlight novel synthetic platforms for the intracellular delivery of siRNAs.
Cell-cell and cell-matrix adhesion in survival and metastasis: Stat3 versus Akt.
Niit M, Hoskin V, Carefoot E … +4 more , Geletu M, Arulanandam R, Elliott B, Raptis L
Biomol Concepts · 2015 Dec · PMID 26565555 · Publisher ↗
Both cell-cell and cell-matrix adhesion are important for epithelial cell differentiation and function. Classical cadherins mediate cell to cell interactions and are potent activators of the signal transducer and activat...
Both cell-cell and cell-matrix adhesion are important for epithelial cell differentiation and function. Classical cadherins mediate cell to cell interactions and are potent activators of the signal transducer and activator of transcription (Stat3), thereby offering survival signaling. While the epithelial (E)-cadherin is required for cells to remain tightly associated within differentiated epithelial tissues, cadherin-11 promotes invasion and metastasis, preferentially to the bone. Cell adhesion to the extracellular matrix is mediated through the integrin receptors that bind to the focal adhesion kinase (FAK)/Src complex, thus activating downstream effectors such as Ras/Erk1/2 and PI3k/Akt, but not Stat3. Therefore, at high densities of cultured cells or in epithelial tissues, co-ordinate activation of the complementary cadherin/Stat3 and integrin/FAK pathways can greatly enhance survival and growth of tumor cells. In neoplastically transformed cells on the other hand, a variety of oncogenes including activated Src or receptor tyrosine kinases, activate both pathways. Still, most single-agent therapies directed against these signaling pathways have proven disappointing in the clinic. Combined targeting of the Src/FAK and Stat3 pathways with inhibitory drugs would be expected to have greater efficacy in inhibiting tumor cell survival, and enhancing sensitivity to conventional cytotoxic drugs for treatment of metastatic disease.
Glyoxalase biochemistry.
Honek JF
Biomol Concepts · 2015 Dec · PMID 26552067 · Publisher ↗
The glyoxalase enzyme system utilizes intracellular thiols such as glutathione to convert α-ketoaldehydes, such as methylglyoxal, into D-hydroxyacids. This overview discusses several main aspects of the glyoxalase system...
The glyoxalase enzyme system utilizes intracellular thiols such as glutathione to convert α-ketoaldehydes, such as methylglyoxal, into D-hydroxyacids. This overview discusses several main aspects of the glyoxalase system and its likely function in the cell. The control of methylglyoxal levels in the cell is an important biochemical imperative and high levels have been associated with major medical symptoms that relate to this metabolite's capability to covalently modify proteins, lipids and nucleic acid.
Recent data concerning heparanase: focus on fibrosis, inflammation and cancer.
Secchi MF, Masola V, Zaza G … +3 more , Lupo A, Gambaro G, Onisto M
Biomol Concepts · 2015 Dec · PMID 26552066 · Publisher ↗
Heparanase (HPSE) is a multitasking protein characterized by enzymatic and non-enzymatic activities. By means of its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans...
Heparanase (HPSE) is a multitasking protein characterized by enzymatic and non-enzymatic activities. By means of its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans, thereby inducing the remodeling of the extracellular matrix and basement membranes. Thanks to the cleavage of HS, HPSE also promotes the release and diffusion of several HS-linked molecules such as growth factors, cytokines and enzymes. In addition to degrading HS chains, HPSE has non-enzymatic functions that trigger several signaling pathways. This signaling activity is achieved by interacting with transmembrane proteins, activating kinases such as Akt and Src, or modulating the activity of factors such as FGF-2 and TGF-β. Several studies have recently highlighted a possible intracellular activity for HPSE, particularly at nuclear level. While HPSE activity is quite limited in physiological conditions, its demonstrated increasing involvement in various pathological conditions, such as in tumor progression and renal disease, have attracted the attention of a growing number of researchers. The fact that no other molecule is capable of performing the same function as HPSE makes this enzyme an attractive potential target of medical treatment. With this short conceptual overview, we aim to provide an update on current knowledge concerning the HPSE protein in the experimental and clinical settings, paying particular attention to its role in fibrosis, inflammation and cancer.
Developments and new vistas in the field of melanocortins.
Leone S, Noera G, Bertolini A
Biomol Concepts · 2015 Dec · PMID 26479351 · Publisher ↗
Melanocortins play a fundamental role in several basic functions of the organism (sexual activity, feeding, inflammation and immune responses, pain sensitivity, response to stressful situations, motivation, attention, le...
Melanocortins play a fundamental role in several basic functions of the organism (sexual activity, feeding, inflammation and immune responses, pain sensitivity, response to stressful situations, motivation, attention, learning, and memory). Moreover, a large body of animal data, some of which were also confirmed in humans, unequivocally show that melanocortins also have impressive therapeutic effects in several pathological conditions that are the leading cause of mortality and disability worldwide (hemorrhagic, or anyway hypovolemic, shock; septic shock; respiratory arrest; cardiac arrest; ischemia- and ischemia/reperfusion-induced damage of the brain, heart, intestine, and other organs; traumatic injury of brain, spinal cord, and peripheral nerves; neuropathic pain; toxic neuropathies; gouty arthritis; etc.). Recent data obtained in animal models seem to moreover confirm previous hypotheses and preliminary data concerning the neurotrophic activity of melanocortins in neurodegenerative diseases, in particular Alzheimer's disease. Our aim was (i) to critically reconsider the established extrahormonal effects of melanocortins (on sexual activity, feeding, inflammation, tissue hypoperfusion, and traumatic damage of central and peripheral nervous system) at the light of recent findings, (ii) to review the most recent advancements, particularly on the effects of melanocortins in models of neurodegenerative diseases, (iii) to discuss the reasons that support the introduction into clinical practice of melanocortins as life-saving agents in shock conditions and that suggest to verify in clinical setting the impressive results steadily obtained with melanocortins in different animal models of tissue ischemia and ischemia/reperfusion, and finally, (iv) to mention the advisable developments, particularly in terms of selectivity of action and of effects.
Trefoil factor family peptides--friends or foes?
Busch M, Dünker N
Biomol Concepts · 2015 Dec · PMID 26479350 · Publisher ↗
Trefoil factor family (TFF) peptides are a group of molecules bearing a characteristic three-loop trefoil domain. They are mainly secreted in mucous epithelia together with mucins but are also synthesized in the nervous...
Trefoil factor family (TFF) peptides are a group of molecules bearing a characteristic three-loop trefoil domain. They are mainly secreted in mucous epithelia together with mucins but are also synthesized in the nervous system. For many years, TFF peptides were only known for their wound healing and protective function, e.g. in epithelial protection and restitution. However, experimental evidence has emerged supporting a pivotal role of TFF peptides in oncogenic transformation, tumorigenesis and metastasis. Deregulated expression of TFF peptides at the gene and protein level is obviously implicated in numerous cancers, and opposing functions as oncogenes and tumor suppressors have been described. With regard to the regulation of TFF expression, epigenetic mechanisms as well as the involvement of various miRNAs are new, promising aspects in the field of cancer research. This review will summarize current knowledge about the expression and regulation of TFF peptides and the involvement of TFF peptides in tumor biology and cancerogenesis.
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