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Current Protein & Peptide Science

Giorgio Cozza, Mauro Salvi
PLK2 and PLK3 are two closely related acidophilic kinases belonging to the Polo-like kinases (PLKs), a family of five members in mammals with a central role in cell cycle and related events. PLK1 is the most investigated enzyme from both physiological and pharmaceutical points of view, however, several specialized cellular functions of PLK2 and PLK3 have been recently discovered paving the way to deepened studies on their biological roles and their feasible selection as future therapeutic targets. Our review aims to provide a summarized view of the current knowledge regarding PLK2 and PLK3 kinases, including substrate specificity and signaling pathways directly affected by these kinases...
January 23, 2018: Current Protein & Peptide Science
Bahram Yavari, Reza Mahjub, Masoud Saidijam, Mojgan Raigani, Meysam Soleimani
Conventional chemotherapeutic drugs have significant limitations: For example, tumors may develop resistance to them, cancers may relapse after treatment, and the drugs may induce secondary malignancies in the treatment of metastatic cancer. There is still a great need for drugs that are able to destroy cancer cells selectively, that is, to effectively treat slow-growing and dormant cells without being affected by chemoresistance mechanisms. A growing number of studies indicate that peptides may be beneficial for drug discovery and development...
January 11, 2018: Current Protein & Peptide Science
Yuki Takechi-Haraya, Hiroyuki Saito
Arginine-rich cell penetrating peptides (CPPs) are very promising drug carriers to deliver membrane-impermeable pharmaceuticals, such as siRNA, bioactive peptides and proteins. CPPs directly penetrate into cells across cell membranes via a spontaneous energy-independent process, in which CPPs appear to interact with acidic lipids in the outer leaflet of the cell membrane. However, acidic lipids represent only 10 to 20% of the total membrane lipid content and in mammalian cell membranes they are predominantly located in the inner leaflet...
January 11, 2018: Current Protein & Peptide Science
Verena Theis, Carsten Theiss
The vascular endothelial growth factor (VEGF) is a homodimeric disulfide bound glycoprotein that promotes endothelial growth, accompanied by higher vascular permeability, and therefore represents an important factor for angiogenesis and vascularization. In addition, VEGF also has a neurotrophic and neuroprotective impact on glial and neuronal cells within the CNS and PNS. Recently, we have shown that VEGF increases somato- and dendritogenesis in neonatal, but not in mature CNS neurons [1], and leads to axonal growth cone guidance during embryonic development of the PNS [2, 3]...
January 3, 2018: Current Protein & Peptide Science
Habibur Rahman, Youngpyo Nam, Jae-Hong Kim, Won-Ha Lee, Kyoungho Suk
Spinal cord circuits play a key role in receiving and transmitting somatosensory information from the body and the brain. They also contribute to the timing and coordination of complex patterns of movement. Under disease conditions, such as spinal cord injury and neuropathic pain, spinal cord circuits receive pain signals from peripheral nerves, and are involved in pain development via neurotransmitters and inflammatory mediators released from neurons and glial cells. Despite the importance of spinal cord circuits in sensory and motor functions, many questions remain regarding the relationship between activation of specific cells and behavioral responses...
December 29, 2017: Current Protein & Peptide Science
Taehun Hong, Kazuki Iwashita, Kentaro Shiraki
Viscosity of protein solution is one of the most troublesome issues for the high-concentration formulation of protein drugs. In this review, we summarize the practical methods that suppress the viscosity of protein solution using small molecular additives. The small amount of salts decreases the viscosity that results from electrostatic repulsion and attraction. The chaotrope suppresses the hydrophobic attraction and cluster formation, which can lower the solution viscosity. Arginine hydrochloride (ArgHCl) also suppresses the solution viscosity due to the hydrophobic and aromatic interactions between protein molecules...
December 12, 2017: Current Protein & Peptide Science
Lisbell D Estrada, Luciana Oliveira-Cruz, Daniel Cabrera
Alzheimer's disease is a neurodegenerative condition affecting millions of people worldwide. Alzheimer's symptoms include memory loss and cognitive decline. Pathologically, the hallmarks of Alzheimer´s are the presence of Amyloid beta-plaques, neurofibrillary tangles, and neuronal loss. Unfortunately, no cure is presently available and current treatments are only symptomatic. Transforming growth factor beta type I (TGF-β1) is a trophic factor involved in neuronal development and synaptic plasticity...
November 28, 2017: Current Protein & Peptide Science
Sebastian Gatica, Claudio Cabello-Verrugio, Felipe Simon
This review includes a comprehensive, but succinct, summary on the essentials of TGF-b structure, family members, receptors, and intracellular mediators. Also provided is a select list of original publications that report novel roles and facets of TGF-b in vascular function and signaling in the contexts of health and disease.
November 27, 2017: Current Protein & Peptide Science
Luciana Scotti, Marcus T Scotti
No abstract text is available yet for this article.
2018: Current Protein & Peptide Science
Ben Dunn
No abstract text is available yet for this article.
2018: Current Protein & Peptide Science
Pratyoosh Shukla
No abstract text is available yet for this article.
2018: Current Protein & Peptide Science
Marco Arrese, Daniel Cabrera, Alejandra Hernandez, Luis Astete, Lisbell Estrada, Claudio Cabello-Verrugio
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide accounting for more than 700 thousand deaths per year. Most of the HCC develops in a cirrhotic liver, a microenvironment where fibrotic tissue replaces parenchymal cells. Thus, there is a close connection between fibrosis and HCC development. Understanding the cellular and molecular mechanisms involved in this process is a crucial step to advance in novel therapeutic or pharmacological strategies to prevent or improve the course of this malignancy...
November 16, 2017: Current Protein & Peptide Science
Tsutomu Arakawa, Masao Tokunaga, Takuya Maruyama, Kentarou Shiraki
MEP (mercapto-ethyl-pyridine) HyperCel is one of the hydrophobic charge induction chromatography (HCIC) resins. Under normal operation, proteins are bound to the MEP resin at neutral pH, at which MEP is not charged, mostly via hydrophobic interaction. MEP has a pyridine group, whose pK is 4.8, and hence is positively charged at acidic pH range. Based on the binding mechanism (i.e., hydrophobic interaction) and the induced positive charge at acidic pH, there may be two ways to elute the bound proteins. One way is to bring the pH down to protonate both MEP resin and the bound protein, leading to charge repulsion and thereby elution...
November 16, 2017: Current Protein & Peptide Science
Larisa Ryskalin, Carla L Busceti, Fiona Limanaqi, Francesca Biagioni, Stefano Gambardella, Francesco Fornai
Alpha synuclein (α-syn) belongs to a class of proteins which are commonly considered to play a detrimental role in neuronal survival. This assumption is based on the occurrence of a severe neuronal degeneration in patients carrying a multiplication of the α-syn gene (SNCA) and in a variety of experimental models, where overexpression of α-syn leads to cell death and neurological impairment. In these conditions, a higher amount of normally structured α-syn produces a damage, which is even worse compared with that produced by α-syn owing an abnormal structure (as occurring following point gene mutations)...
November 16, 2017: Current Protein & Peptide Science
Johanna Abrigo, Felipe Simon, Daniel Cabrera, Gonzalo Cordova, Capucine Trollet, Claudio Cabello Verrugio
Among the soluble factors that regulate skeletal muscle function, Transforming Growth Factor type Beta 1 (TGF-b1) is one of the most studied. This factor inhibits myogenesis and regeneration by regulating the activity and function of satellite cells (SCs). Indeed, TGF-b has a central role in muscle pathologies in which there is development of fibrosis and/or atrophy of skeletal muscle. Thus, in this review we present the critical and recent antecedents regarding the mechanisms and cellular targets involved in the effects of TGF-b1 in the muscle, in pathological processes such as the inhibition of regeneration, fibrosis and atrophy...
November 16, 2017: Current Protein & Peptide Science
Jelena Krstic, Drenka Trivanovic, Hristina Obradovic, Tamara Kukolj, Diana Bugarski, Juan F Santibanez
The ability to differentiate into cells of different lineage, such as muscle, bone, cartilage and fat, is the chief value of adult mesenchymal stem cells (MSCs) which can be used with the final aim to regenerate damaged tissue. Due to potential use, as well as importance in tissue development, a number of questions have been raised regarding the molecular mechanisms of MSC differentiation. As one of the crucial mediators in organism development, transforming growth factor beta (TGF-β) superfamily directs MSCs commitment in the selection of differentiation pathways...
November 16, 2017: Current Protein & Peptide Science
Charlotte Cabanne, Xavier Santarelli
Mixed mode chromatography resins with salt tolerance, large design space and orthogonal selectivity requires a slightly more complex development than traditional resins. It is important to screen several ligands and several binding and elution conditions. This allows taking full advantage of these resins. High-Throughput Screening (HTS) for Process Development should be done with the help of Design of Experiment (DoE). It could be performed in filter plates or Robocolumns, and assisted by liquid handling automated workstation...
October 29, 2017: Current Protein & Peptide Science
Andrea Bellelli
Hemoglobin (Hb) is the prototypical example of a cooperative protein. Cooperativity of Hb is largely accounted for by an allosteric structural change between the T and R quaternary structures. Allostery is such a powerful explanation of Hb cooperativity that the possibility of cooperative events occurring within each allosteric conformation, in the absence of any quaternary structural change has usually been overlooked, and actually experiments specifically aimed at detecting non-allosteric cooperativity have usually failed to do so...
October 29, 2017: Current Protein & Peptide Science
Juan F Santibanez, Jelena Krstic
Transforming growth factor beta (TGF-β) is well recognized as playing a double role in tumor progression. Its antitumor role takes place in the early stages of caner development, when TGF-β acts as a repressor of epithelial tumor growth. In advanced stages of cancer development, TGF-β has a tumor stimulating role, acting concomitantly with the increase of cancer cell migration and metastasis. One of the critical features of cancer cells is their ability to migrate and invade the surrounding tissues leading to metastases in different organs...
October 29, 2017: Current Protein & Peptide Science
Elizabeth A Kulikova, Alexander V Kulikov
Kaiso is a bimodal transcriptional repressor. It binds methylated CpG islands or the sequence-specific consensus in the DNA molecule with the Kaiso zinc-finger domain and recruits repressive protein complexes to these DNA fragments by the interaction of the BTB/POZ domain with the complex of NCoR1 corepressor and histone deacetylase, thereby performing transcription repression. Kaiso is involved in epigenetic regulation of transcription. Moreover, the complex Kaiso and catenin p120ctn modulates the transcription of the Wnt-target genes...
October 29, 2017: Current Protein & Peptide Science
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