Warsaw, Poland

The Nencki Institute of Experimental Biology is a Polish scientific research organization and a part of Polish Academy of science headquartered in Warsaw, Poland. Founded in 1918, it is a leading institution in the country in the field of neurobiology, molecular biology and biochemistry. Wikipedia.

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Lukasiuk K.,Nencki Institute of Experimental Biology | Becker A.J.,University of Bonn
Neurotherapeutics | Year: 2014

Epileptogenesis, a process leading to a reduced threshold for seizures after transient brain insults, as well as the mechanisms underlying the propensity to generate spontaneous epileptic seizures, are highly dynamic processes. Biomarkers-objective measures of biological processes-would be excellent tools for monitoring epileptogenesis and the dynamics of increased seizure propensity, as well as the potential to interfere, for example pharmacologically, with these key pathological aspects of epilepsy. Molecular biomarkers have revolutionized therapies, as well as response prediction and monitoring of therapies in other biomedical fields. However, high-impact molecular biomarkers are still not available in the context of epilepsy. Several factors, such as the large heterogeneity of epileptic syndromes and their underlying pathological patterns, as well as the limited availability of tissue samples, represent a particular challenge to the development of molecular biomarkers in epileptogenesis and epilepsy. However, substantial technical progress has been made recently with respect to biomarker characterization and monitoring by large throughput analysis on the genomic, mRNA, and proteomic levels, starting from minute amounts of brain tissue or body fluids, for example cerebrospinal fluid, blood, serum, or plasma. Given the substantial cellular- and network-level functional pathophysiology involved in epilepsy, it may be beneficial in the future to combine molecular analysis with other methods, such as imaging and electrophysiological biomarkers. © 2014 The Author(s).

Liguz-Lecznar M.,Nencki Institute of Experimental Biology
Neural plasticity | Year: 2013

Age-related brain injuries including stroke are a leading cause of morbidity and mental disability worldwide. Most patients who survive stroke experience some degree of recovery. The restoration of lost functions can be explained by neuronal plasticity, understood as brain ability to reorganize and remodel itself in response to changed environmental requirements. However, stroke triggers a cascade of events which may prevent the normal development of the plastic changes. One of them may be inflammatory response initiated immediately after stroke, which has been found to contribute to neuronal injury. Some recent evidence though has suggested that inflammatory reaction can be also neuroprotective. This paper attempts to discuss the influence of poststroke inflammatory response on brain plasticity and stroke outcome. We also describe the recent anti-inflammatory strategies that have been effective for recovery in experimental stroke.

Dobrzyn P.,Nencki Institute of Experimental Biology
American journal of physiology. Endocrinology and metabolism | Year: 2013

Cardiac hypertrophy is accompanied by molecular remodeling that affects different cellular pathways, including fatty acid (FA) utilization. In the present study, we show that cardiac lipid metabolism is differentially regulated in response to physiological (endurance training) and pathological [abdominal aortic banding (AAB)] hypertrophic stimuli. Physiological hypertrophy was accompanied by an increased expression of lipogenic genes and the activation of sterol regulatory element-binding protein-1c and Akt signaling. Additionally, FA oxidation pathways regulated by AMP-activated protein kinase (AMPK) and peroxisome proliferator activated receptor-α (PPARα) were induced in trained hearts. Cardiac lipid content was not changed by physiological stimulation, underlining balanced lipid utilization in the trained heart. Moreover, pathological hypertrophy induced the AMPK-regulated oxidative pathway, whereas PPARα and expression of its downstream targets, i.e., acyl-CoA oxidase and carnitine palmitoyltransferase I, were not affected by AAB. In contrast, pathological hypertrophy leads to cardiac triglyceride (TG) and diacylglycerol (DAG) accumulation, although the expression of lipogenic genes and the levels of FA transport proteins (CD36 and FATP) were not changed or reduced compared with the sham group. A possible explanation for this phenomenon is a decrease in lipolysis, as evidenced by the increased content of adipose triglyceride lipase inhibitor G0S2, the increased phosphorylation of hormone-sensitive lipase at Ser(565), and the decreased protein levels of DAG lipase that attenuate TG and DAG contents. The increased TG and DAG accumulation observed in AAB-induced hypertrophy might have lipotoxic effects, thereby predisposing to cardiomyopathy and heart failure in the future.

Wilczynski G.M.,Nencki Institute of Experimental Biology
Neuropharmacology | Year: 2014

Recent studies in neurons indicate that the large-scale chromatin architectural framework, including chromosome territories or lamina-associated chromatin, undergoes dynamic changes that represent an emergent level of regulation of neuronal gene-expression. This phenomenon has been implicated in neuronal differentiation, long-term potentiation, seizures, and disorders of neural plasticity such as Rett syndrome and epilepsy. This article is part of the Special Issue entitled 'Neuroepigenetic Disorders'. © 2014 Elsevier Ltd. All rights reserved.

Wrzosek A.,Nencki Institute of Experimental Biology
Cell Calcium | Year: 2014

NS1619 (1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazole-2-one) is widely used as a large-conductance Ca2+-activated K+ (BKCa) channel opener. It was previously reported that activation of BKCa channels by NS1619 could protect the cardiac muscle against ischaemia and reperfusion injury. This study reports the effects of NS1619 on intracellular Ca2+ homeostasis in H9C2 and C2C12 cells as well as its molecular mechanism of action. The effects of NS1619 on Ca2+ homeostasis in C2C12 and H9C2 cells were assessed using the Fura-2 fluorescence method. Ca2+ uptake by sarcoplasmic reticulum (SR) vesicles isolated from rat skeletal muscles and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity were measured. The effect of NS1619 on the isometric force of papillary muscle contraction in the guinea pig heart was also examined. H9C2 and C2C12 cells treated with NS1619 released Ca2+ from internal stores in a concentration-dependent manner. Ca2+ accumulation by the SR vesicles was inhibited by NS1619 treatment. NS1619 also decreased the activity of SERCA derived from rat skeletal muscle. The calcium release from cell internal stores and inhibition of SERCA by NS1619 are pH dependent. Finally, NS1619 had a profound effect on the isometric force of papillary muscle contraction in the guinea pig heart. These results indicate that NS1619 is a potent modulator of the intracellular Ca2+ concentration in H9C2 and C1C12 cells due to its interaction with SRs. The primary target of NS1619 is SERCA, which is located in SR vesicles. The effect of NS1619-mediated SERCA inhibition on cytoprotective processes should be considered. © 2014 Elsevier Ltd.

Sikora E.,Nencki Institute of Experimental Biology
Experimental Gerontology | Year: 2013

Cellular senescence is the state of permanent inhibition of cell proliferation. Replicative senescence occurs due to the end replication problem and shortening telomeres with each cell division leading to DNA damage response (DDR). The number of short telomeres increases with age and age-related pathologies. Stress induced senescence, although not accompanied by attrition of telomeres, is also attributed to the DDR induced by irreparable DNA lesions in telomeric DNA. Senescent cells characterized by the presence of γH2AX, the common marker of double DNA strand breaks, and other senescence markers including activity of SA-β-gal, accumulate in tissues of aged animals and humans as well as at sites of pathology. It is believed that cellular senescence evolved as a cancer barrier since non-proliferating senescent cells cannot be transformed to neoplastic cells. On the other hand senescent cells favor cancer development, just like other age-related pathologies, by creating a low grade inflammatory state due to senescence associated secretory phenotype (SASP). Reversal/inhibition of cellular senescence could prolong healthy life span, thus many attempts have been undertaken to influence cellular senescence. The two main approaches are genetic and pharmacological/nutritional modifications of cell fate. The first one concerns cell reprogramming by induced pluripotent stem cells (iPSCs), which in vitro is effective even in cells undergoing senescence, or derived from very old or progeroid patients. The second approach concerns modification of senescence signaling pathways just like TOR-induced by pharmacological or with natural agents. However, knowing that aging is unavoidable we cannot expect its elimination, but prolonging healthy life span is a goal worth serious consideration. © 2012 Elsevier Inc.

Pitkanen A.,University of Eastern Finland | Lukasiuk K.,Nencki Institute of Experimental Biology
The Lancet Neurology | Year: 2011

Prevention of epileptogenesis after brain trauma is an unmet medical challenge. Recent molecular profiling studies have provided an insight into molecular changes that contribute to formation of ictogenic neuronal networks, including genes regulating synaptic or neuronal plasticity, cell death, proliferation, and inflammatory or immune responses. These mechanisms have been targeted to prevent epileptogenesis in animal models. Favourable effects have been obtained using immunosuppressants, antibodies blocking adhesion of leucocytes to endothelial cells, gene therapy driving expression of neurotrophic factors, pharmacological neurostimulation, or even with conventional antiepileptic drugs by administering them before the appearance of genetic epilepsy. Further studies are needed to clarify the optimum time window and aetiological specificity of treatments. Questions related to adverse events also need further consideration. Encouragingly, the recent experimental studies emphasise that the complicated process of epileptogenesis can be favourably modified, and that antiepileptogenesis as a treatment indication might not be an impossible mission. © 2011 Elsevier Ltd.

Dzik J.M.,Nencki Institute of Experimental Biology
Acta Biochimica Polonica | Year: 2010

The last two decades of study enriched greatly our knowledge of how the immune system originated and the sophisticated immune mechanisms of today's vertebrates and invertebrates developed. Even unicellular organisms possess mechanisms for pathogen destruction and self recognition. The ability to distinguish self from non-self is a prerequisite for recognition of sexual compatibility and ensuring survival. Molecules involved in these processes resemble those found in the phagocytic cells of higher organisms. Recognition of bacteria by scavenger receptors induces phagocytosis or endo-cytosis. The phagocytic mechanisms characterizing the amoeboid protozoans developed further during the evolution towards innate immunity. The scavenger receptor cysteine-rich domain SRCR is encoded in the genomes from the most primitive sponges to mammals. The immune system of sponges comprises signal transduction molecules which occur in higher metazoans as well. Sponges already possess recognition systems for pathogenic bacteria and fungi, based on membrane receptors (a lipopolysaccharide-interacting protein, a cell surface receptor recognizing β(1 -→3)-D-glucans of fungi). Perforin-like molecules and lysozymes are involved, among others, in defense in sponges. Reactive oxygen and nitrogen species function in the immunity of early metazoan. Genes encoding the family of reactive oxygen-generating NADPH oxidases (Noxes) are found in a variety of protists and plants. The NO synthases of cni-darians, mollusks, and chordates are conserved with respect to the mammalian NOS. The antimicrobial peptides of protozoans, amoebapores, are structural and functional analogs of the natural killer cell peptide, NK-lysin, of vertebrates. An ancestral S-type lectin has been found in sponges. Opsonizing properties of lectins and the ability to agglutinate cells justify their classification as primitive recognition molecules. Invertebrate cytokines are not homologous to those of vertebrate, and their functional convergence was presumably enabled by the general similarity of the lectin-like recognition domain three-dimensional structure. Sponges contain molecules with SCR/CCP domains that show high homology to the mammalian regulators of complement activation (RCA family). A multi-component complement system comprising at least the central molecule of the complement system, C3, Factor B, and MASP developed in the cnidarians and evolved into the multilevel cascade engaged in innate and acquired immunity of vertebrates. The adaptive immune system of mammals is also deeply rooted in the metazoan evolution. Some its precursors have been traced as deep as in sponges, namely, two classes of receptors that comprise Ig-like domains, the receptor tyrosine kinases (RTK), and the non-enzymic sponge adhesion molecules (SAM). The antibody-based immune system defined by the presence of the major histocompatibility complex (MHC), T-cell receptor (TCR), B-cell receptor (BCR) or recombination activating genes (RAGs) is known beginning from jawed fishes. However, genes closely resembling RAG1 and RAG2 have been uncovered in the genome of a see urchin. The ancestry of MHC gene remains unknown. Similarly, no homologue of the protein binding domain (PBD) in MHC molecules has been found in invertebrates. The pathway by which endogenous peptides are degraded for presentation with class I MHC molecules utilizes mechanisms similar to those involved in the normal turnover of intracellular proteins, apparently recruited to work also for the immune system. Several cDNAs coding for lysosomal enzymes, e.g., cathepsin, have been isolated from sponges. All chromosomal duplication events in the MHC region occurred after the origin of the agnathans but before the gnathostomes split from them. The V-domains of the subtype found in the receptors of T and B-cells are known from both agnathans and cephalochordates, although they do not rearrange. The rearrangement mechanism of the lymphocyte V-domains suggests its origin from a common ancestral domain existing before the divergence of the extant gnathostome classes. Activation-induced deaminase (AID) - homologous proteins have been found only in the gnathostomes. It appears thus that the adaptive immunity of vertebrates is a result of stepwise accumulation of small changes in molecules, cells and organs over almost half a billion years.

Dziembowska M.,Nencki Institute of Experimental Biology | Wlodarczyk J.,Nencki Institute of Experimental Biology
International Journal of Biochemistry and Cell Biology | Year: 2012

Matrix metalloproteinase-9 (MMP-9), an extracellularly acting, Zn 2+-dependent endopeptidase is a subject to complex regulation at the level of transcription, mRNA dendritic translocation, and local translation as well as protein activation, as it is released extracellularly in a latent, pro-form with the enzymatic site covered by a propeptide that has to be cleaved off to reveal the activity. In neurons, MMP-9 is present at the postsynaptic domains of excitatory synapses. Here, we review the role of MMP-9 in induction of structural dendritic spine modifications and in synaptic plasticity. In particular, we focus on local translation, activity-dependent secretion and activation of MMP-9 leading to its role in long term potentiation and regulation of remodeling of dendritic spines. © 2012 Elsevier Ltd. All rights reserved.

Nencki Institute of Experimental Biology | Date: 2014-05-16

Isolated peptides, compositions and methods of use for treating tumors infiltrated with macrophages, such as glioblastomas.

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