| 1. |
|
|
| 2. |
- Fisher, Linda, et al.
(författare)
-
Targeting cytokine expression in glial cells by cellular delivery of an NFκB decoy
- 2007
-
Ingår i: Journal of Molecular Neuroscience. - 0895-8696 .- 1559-1166. ; 31:3, s. 209-219
-
Tidskriftsartikel (refereegranskat)abstract
- Inhibition of nuclear factor (NF)-κB has emerged as an important strategy for design of anti-inflammatory therapies. In neurodegenerative disorders like Alzheimer’s disease, inflammatory reactions mediated by glial cells are believed to promote disease progression. Here, we report that uptake of a double-stranded oligonucleotide NF-κB decoy in rat primary glial cells is clearly facilitated by noncovalent binding to a cell-penetrating peptide, transportan 10, via a complementary peptide nucleic acid (PNA) sequence. Fluorescently labeled oligonucleotide decoy was detected in the cells within 1 h only when cells were incubated with the decoy in the presence of cell-penetrating peptide. Cellular delivery of the decoy also inhibited effects induced by a neurotoxic fragment of the Alzheimer β amyloid peptide in the presence of the inflammatory cytokine interleukin (IL) 1β. Pretreatment of the cells with the complex formed by the decoy and the cell-penetrating peptide-PNA resulted in 80% and 50% inhibition of the NF-κB binding activity and IL-6 mRNA expression, respectively.
|
|
| 3. |
- Arukuusk, Piret, et al.
(författare)
-
New generation of efficient peptide-based vectors, NickFects, for the delivery of nucleic acids
- 2013
-
Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : Elsevier BV. - 0005-2736 .- 1879-2642. ; 1828:5, s. 1365-1373
-
Tidskriftsartikel (refereegranskat)abstract
- Harnessing of a branched structure is a novel approach in the design of cell-penetrating peptides and it has provided highly efficient transfection reagents for intracellular delivery of nucleic acids. The new stearylated TP10 analogs, NickFects, condense plasmid DNA, splice correcting oligonucleotides and short interfering RNAs into stable nanoparticles with a size of 62-160 nm. Such nanoparticles have a negative surface charge (-11 to -18 mV) in serum containing medium and enable highly efficient gene expression, splice correction and gene silencing. One of the novel peptides, NickFect51 is capable of transfecting plasmid DNA into a large variety of cell lines, including refractory suspension and primary cells and in several cases exceeds the transfection level of commercially available reagent Lipofectamine (TM) 2000 without any cytotoxic side effects. Additionally we demonstrate the advantages of NickFect51 in a protein production system, QMCF technology, for expression and production of recombinant proteins in hardly transfectable suspension cells.
|
|
| 4. |
- Freimann, Krista, et al.
(författare)
-
Galanin receptors as a potential target for neurological disease
- 2015
-
Ingår i: Expert opinion on therapeutic targets. - : Informa UK Limited. - 1472-8222 .- 1744-7631. ; 19:12, s. 1665-1676
-
Forskningsöversikt (refereegranskat)abstract
- INTRODUCTION: Galanin is a 29/30 amino acid long neuropeptide that is widely expressed in the brains of many mammals. Galanin exerts its biological activities through three different G protein-coupled receptors, GalR1, GalR2 and GalR3. The widespread distribution of galanin and its receptors in the CNS and the various physiological and pharmacological effects of galanin make the galanin receptors attractive drug targets.AREAS COVERED: This review provides an overview of the role of galanin and its receptors in the CNS, the involvement of the galaninergic system in various neurological diseases and the development of new galanin receptor-specific ligands.EXPERT OPINION: Recent advances and novel approaches in migrating the directions of subtype-selective ligand development and chemical modifications of the peptide backbone highlight the importance of the galanin neurochemical system as a potential target for drug development.
|
|
| 5. |
- Holm, Tina, et al.
(författare)
-
Cell-penetrating peptides as antifungals towards Malassezia sympodialis
- 2012
-
Ingår i: Letters in Applied Microbiology. - 0266-8254 .- 1472-765X. ; 54:1, s. 39-44
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To determine whether different antimicrobial peptides (AMPs) and cell-penetrating peptides (CPPs) are able to inhibit the growth of the commensal yeast Malassezia sympodialis, which can act as a trigger factor in different skin disorders, such as atopic eczema (AE), seborrhoeic eczema (SE) and dandruff. Methods and results: The antifungal activity of 21 different AMPs and CPPs was investigated by microdilution assay and plate counting to determine the number of colony forming units. Five CPPs and one AMP showed fungicidal activity at submicromolar concentrations. Importantly, no membrane damage on human keratinocytes was detected after peptide treatment. Conclusions: Several CPPs, while being nontoxic to mammalian cells, possess growth inhibitory activity on the very stringent yeast M. sympodialis. Significance and impact of study: Our findings that the CPPs and one AMP that are harmless towards mammalian cells act as antifungal agents against sympodialis opens up the possibility to use these in the treatment for AL, SE and dandruff. To our knowledge, this is the first time peptides have been identilied as antilungal agents against sympodialis. Further studies to ekicidate the mechanism are warranted.
|
|
| 6. |
- Pärnaste, Ly, et al.
(författare)
-
Methods to follow intracellular trafficking of cell-penetrating peptides
- 2016
-
Ingår i: Journal of drug targeting (Print). - 1061-186X .- 1029-2330. ; 24:6, s. 508-519
-
Tidskriftsartikel (refereegranskat)abstract
- Cell-penetrating peptides (CPPs) are efficient vehicles to transport bioactive molecules into the cells. Despite numerous studies the exact mechanism by which CPPs facilitate delivery of cargo to its intracellular target is still debated. The current work presents methods that can be used for tracking CPP/pDNA complexes through endosomal transport and show the role of endosomal transport in the delivery of cargo. Separation of endosomal vesicles by differential centrifugation enables to pinpoint the localization of delivered cargo without labeling it and gives important quantitative information about pDNA trafficing in certain endosomal compartments. Single particle tracking (SPT) allows following individual CPP/cargo complex through endosomal path in live cells, using fluoresently labled cargo and green fluoresent protein expressing cells. These two different methods show similar results about tested NickFect/pDNA complexes intracellular trafficing. NF51 facilitates rapid internalization of complexes into the cells, prolongs their stay in early endosomes and promotes release to cytosol. NF1 is less capable to induce endosomal release and higher amount of complexes are routed to lysosomes for degradation. Our findings offer potential delivery vector for in vivo applications, NF51, where endosomal entrapment has been allayed. Furthermore, these methods are valuable tools to study other CPP-based delivery systems.
|
|
| 7. |
- Raeaegel, Helin, et al.
(författare)
-
Cell-penetrating peptide secures an efficient endosomal escape of an intact cargo upon a brief photo-induction
- 2013
-
Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 70:24, s. 4825-4839
-
Tidskriftsartikel (refereegranskat)abstract
- Since their discovery, cell-penetrating peptides (CPPs) have provided a novel, efficient, and non-invasive mode of transport for various (bioactive) cargos into cells. Despite the ever-growing number of successful implications of the CPP-mediated delivery, issues concerning their intracellular trafficking, significant targeting to degradative organelles, and limited endosomal escape are still hindering their widespread use. To overcome these obstacles, we have utilized a potent photo-induction technique with a fluorescently labeled protein cargo attached to an efficient CPP, TP10. In this study we have determined some key requirements behind this induced escape (e.g., dependence on peptide-to-cargo ratio, time and cargo), and have semi-quantitatively assessed the characteristics of the endosomes that become leaky upon this treatment. Furthermore, we provide evidence that the photo-released cargo remains intact and functional. Altogether, we can conclude that the photo-induced endosomes are specific large complexes-condensed non-acidic vesicles, where the released cargo remains in its native intact form. The latter was confirmed with tubulin as the cargo, which upon photo-induction was incorporated into microtubules. Because of this, we propose that combining the CPP-mediated delivery with photo-activation technique could provide a simple method for overcoming major limitations faced today and serve as a basis for enhanced delivery efficiency and a subsequent elevated cellular response of different bioactive cargo molecules.
|
|
| 8. |
- Abdelhamid, Hani Nasser, et al.
(författare)
-
Carbonized chitosan encapsulated hierarchical porous zeolitic imidazolate frameworks nanoparticles for gene delivery
- 2020
-
Ingår i: Microporous and Mesoporous Materials. - : Elsevier BV. - 1387-1811 .- 1873-3093. ; 302
-
Tidskriftsartikel (refereegranskat)abstract
- Hierarchical mesoporous carbon (MPC) nanomaterials derived from the carbonized chitosan (CTS) encapsulated zeolitic imidazolate frameworks (ZIF-8) is synthesized and applied for gene delivery. The synthesis of ZIF-8 is achieved at room temperature using water as a solvent in the presence of CTS within 60 min. The synthesis method offered a hierarchical porous structure of ZIF-8. The carbonization of the prepared materials leads to the formation of MPC nanomaterials. MPC materials were applied as a non-viral vectors for gene delivery using two oligonucleotides (ONs) called Luciferase-expressing plasmid (pGL3), and splice correction oligonucleotides (SCO). The materials are biocompatible and showed insignificant toxicity. The transfection using MPC with and without cell-penetrating peptides (CPPs) was reported. MPC improved the transfection efficiency of CPPs (PepFect 14 (PF-14), and PF-221) by 10 fold due to the synergistic effect of MCP and CPPs. The reasonable mechanism for the cell transfection using these new vectors was also highlighted.
|
|
| 9. |
- Abdelhamid, Hani Nasser, et al.
(författare)
-
Gene delivery using cell penetrating peptides-zeolitic imidazolate frameworks
- 2020
-
Ingår i: Microporous and Mesoporous Materials. - : Elsevier BV. - 1387-1811 .- 1873-3093. ; 300
-
Tidskriftsartikel (refereegranskat)abstract
- Cell-penetrating peptides (CPPs), and metal-organic frameworks (MOFs) are promising as next-generation for the delivery of gene-based therapeutic agents. Oligonucleotide (ON)-mediated assembly of nanostructures composed of hierarchical porous zeolitic imidazolate framework (ZIF-8), and nanoparticles such as graphene oxide (GO), and magnetic nanoparticles (MNPs) for gene therapy are reported. Five different types of non-viral vectors (ZIF-8, RhB@ZIF-8, BSA@ZIF-8, MNPs@ZIF-8, and GO@ZIF-8), and three gene therapeutic agents (plasmid, splice correction oligonucleotides (SCO), and small interfering RNA (siRNA)) were investigated. The polyplexes were characterized and applied for gene transfection. The materials show very low toxicity with high efficiency for luciferase transfection. ZIF-8 enhances the transfection of plasmid, SCO, siRNA of CPPs by 2-8 folds. The mechanism of the cell uptakes was also highlighted. Data reveal cell internalization via scavenger class A (SCARA).
|
|
| 10. |
- Ajayi, Abiodun, et al.
(författare)
-
Expanded ataxin-7 cause toxicity by inducing ROS production from NADPH oxidase complexes in a stable inducible Spinocerebellar ataxia type 7 (SCA7) model
- 2012
-
Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 13
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Spinocerebellar ataxia type 7 (SCA7) is one of nine inherited neurodegenerative disorders caused by polyglutamine (polyQ) expansions. Common mechanisms of disease pathogenesis suggested for polyQ disorders include aggregation of the polyQ protein and induction of oxidative stress. However, the exact mechanism(s) of toxicity is still unclear. Results: In this study we show that expression of polyQ expanded ATXN7 in a novel stable inducible cell model first results in a concomitant increase in ROS levels and aggregation of the disease protein and later cellular toxicity. The increase in ROS could be completely prevented by inhibition of NADPH oxidase (NOX) complexes suggesting that ATXN7 directly or indirectly causes oxidative stress by increasing superoxide anion production from these complexes. Moreover, we could observe that induction of mutant ATXN7 leads to a decrease in the levels of catalase, a key enzyme in detoxifying hydrogen peroxide produced from dismutation of superoxide anions. This could also contribute to the generation of oxidative stress. Most importantly, we found that treatment with a general anti-oxidant or inhibitors of NOX complexes reduced both the aggregation and toxicity of mutant ATXN7. In contrast, ATXN7 aggregation was aggravated by treatments promoting oxidative stress. Conclusion: Our results demonstrates that oxidative stress contributes to ATXN7 aggregation as well as toxicity and show that anti-oxidants or NOX inhibition can ameliorate mutant ATXN7 toxicity.
|
|
