Most Cited Article: The Role of ABC Transporters in Protecting Cells from Bilirubin Toxicity

---

The Role of ABC Transporters in Protecting Cells from Bilirubin Toxicity

Author(s):

C. Bellarosa, G. Bortolussi and C. TiribelliPages 2884-2892 (9)

Abstract:

The ATP-Binding Cassette (ABC) superfamily is the largest transporter family known to translocate a wide variety of exogenous and endogenous substrates across cell membranes. In this chapter we review the potential role of three ABC proteins in the transport of unconjugated bilirubin (UCB). These transporters are MRP1, MRP3 and PGP (MDR1). MRP1 is expressed at high levels in most epithelia, usually at the basolateral membrane. Among a multiplicity of substrates, MRP1 mediates the ATP-dependent cellular export of UCB, and its role has been demonstrated in protecting cells from UCB toxicity. MRP3 is an organic anion transporter whose major substrates are GSH conjugates of organic compounds. Among the MRP family members, MRP3 shares the highest degree of amino acid homology with MRP1. Although the hepatic expression of MRP3 has been reported to be up-regulated by bilirubin and bilirubin glucuronides, it is unknown whether MRP3 is also involved in the transport of UCB. PGP is expressed in organs involved in the elimination of endo- and xenobiotics and UCB is one of these substrates. Since the Km of PGP for UCB is well above pathophysiological levels of Bf, it remains uncertain whether it has a role in protecting against UCB cytotoxicity.

Keywords:

ATP-binding-cassette protein (ABC) protein, multidrug-resistance-associated protein 1 (MRP1), multidrugresistance-associated protein 3 (MRP3), P-glycoprotein (PGP), unconiugated bilirubin, bilirubin neurocytotoxicity

Affiliation:

Centro Studi Fegato, Bldg Q -AREA Science Park Basovizza, SS14 Km 163,5, 34012 Trieste, Italy.

Read Full-Text article

For More Information Please Visit Our Website Current Pharmaceutical Design

Read More

AFM-Based Single Molecule Techniques: Unraveling the Amyloid Pathogenic Species

AFM-Based Single Molecule Techniques: Unraveling the Amyloid Pathogenic Species

Author(s):

Francesco Simone Ruggeri, Johnny Habchi, Andrea Cerreta and Giovanni DietlerPages 3950-3970 (21)

Abstract:

Background: A wide class of human diseases and neurodegenerative disorders, such as Alzheimer’s disease, is due to the failure of a specific peptide or protein to keep its native functional conformational state and to undergo a conformational change into a misfolded state, triggering the formation of fibrillar cross-β sheet amyloid aggregates. During the fibrillization, several coexisting species are formed, giving rise to a highly heterogeneous mixture. Despite its fundamental role in biological function and malfunction, the mechanism of protein self-assembly and the fundamental origins of the connection between aggregation, cellular toxicity and the biochemistry of neurodegeneration remains challenging to elucidate in molecular detail. In particular, the nature of the specific state of proteins that is most prone to cause cytotoxicity is not established. Methods: In the present review, we present the latest advances obtained by Atomic Force Microscopy (AFM) based techniques to unravel the biophysical properties of amyloid aggregates at the nanoscale. Unraveling amyloid single species biophysical properties still represents a formidable experimental challenge, mainly because of their nanoscale dimensions and heterogeneous nature. Bulk techniques, such as circular dichroism or infrared spectroscopy, are not able to characterize the heterogeneity and inner properties of amyloid aggregates at the single species level, preventing a profound investigation of the correlation between the biophysical properties and toxicity of the individual species. Conclusion: The information delivered by AFM based techniques could be central to study the aggregation pathway of proteins and to design molecules that could interfere with amyloid aggregation delaying the onset of misfolding diseases.

Keywords:

Misfolding diseases, Alzheimer’s disease, amyloid, protein aggregation, single molecule biophysics, afm, nanomechanical properties, infrared nanospectroscopy.

Affiliation:

Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, United Kingdom.

Read Full-Text article

For More Information Please click here

Current Pharmaceutical Design

Read More

The Microbial Quality Aspects and Decontamination Approaches for the Herbal Medicinal Plants and Products: An in-Depth Review

---

The Microbial Quality Aspects and Decontamination Approaches for the Herbal Medicinal Plants and Products: An in-Depth Review

[ Vol. 22 , Issue. 27 ]

Author(s):

Daniela Dal Molim Ghisleni, Marina de Souza Braga, Irene Satiko Kikuchi, Mirela Braşoveanu, Monica R. Nemţanu, Kamal Dua and Terezinha de Jesus Andreoli PintoPages 4264-4287 (24)

Abstract:

Background: The present review article provides an overview of the published literature concerning microbial quality of medicinal plants and products and their decontamination methods. It is important to analyze different aspects regarding the cultivation, growing, harvesting, storage, manufacturing, and decontamination of medicinal plant products. Herbal medicinal plants bear a massive microbial load leading to contamination and mycotoxin, which needs to be considered, and properly controlled using suitable sterilization and decontamination methods. Methods: The main focus of this review is on the definition, advantages, disadvantages and applications of decontamination methods, particularly to show that one must consider the characteristics of the initial sample to be decontaminated. Results: The effects of various methods (ozone, plasma, irradiation) on medicinal herbs and products treated for microbiological decontamination are dependent on factors related to microbial load (i.e., nature and amount of initial contamination), herb/product matrix (i.e., complexity of chemical composition, physical state - solid or liquid) and treatment conditions (i.e., time, irradiation dose, absence or presence of oxygen). In addition, it is important to accept some loss of the chemical compounds, while decreasing microbial load to acceptable limits according to official herbal pharmacopoeias and literature, thus ensuring a final product with quality, safety and therapeutic efficacy. Conclusion: The conclusion, which comes from this contribution, is that herbal medicine has more contaminants than a chemically welldefined drug, thus, good manufacturing practices should be followed.

Keywords:

Herbal medicinal plants, herbal medicinal products, microbiological contamination, bio-burden, quality, decontamination, GMP.

Affiliation:

Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Rua Professor Lineu Prestes 05508-000, Cidade Universitária, Brazil.

Read Full-Text article

Read More

Upcoming Thematic Issue – Cardiovascular Prevention: Can We Do Any Better

courtesy by Bentham Insight

Read More

New Issue ::: Current Pharmaceutical Design , 22 Issue 27

Current Pharmaceutical Design publishes timely in-depth reviews and research articles from leading pharmaceutical researchers in the field, covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area guest edited by an acknowledged authority in the field.

Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design including: medicinal chemistry, pharmacology, drug targets and disease mechanism

Articles from the journal Current Pharmaceutical Design , 22 Issue 27

• Editorial (Thematic Issue: Perspectives and Challenges in Rational Exploitation of Phytochemicals in Cure, Control and Management of Diseases)
• Phytochemicals: Potential in Management of Climacteric Neurobiology
• Phytochemicals as Inhibitors of Candida Biofilm
• Challenges in the Development of Antifungal Agents Against Candida: Scope of Phytochemical Research
• Historical Spice as a Future Drug: Therapeutic Potential of Piperlongumine
• Anticancer Potential of Ginger: Mechanistic and Pharmaceutical Aspects
• NF-κB Blockers Gifted by Mother Nature: Prospectives in Cancer Cell Chemosensitization
• Phytochemicals as Adjunctive with Conventional Anticancer Therapies
• Nanomedicine as a Strategy for Natural Compound Delivery to Prevent and Treat Cancers
• Exploring Nanotechnologies for the Effective Therapy of Malaria Using Plant-Based Medicines
• Lipid Based Nanosystems for Curcumin: Past, Present and Future
• Microemulsion and Microemulsion-Based Gels for Topical Antifungal Therapy with Phytochemicals
• The Microbial Quality Aspects and Decontamination Approaches for the Herbal Medicinal Plants and Products: An in-Depth Review
• Current Perspective in the International Trade of Medicinal Plants Material: An Update

For details on the articles, please visit this link :: http://bit.ly/2bwY2Bu 

courtesy by : Bentham Insight

Read More

Current Pharmaceutical Design , 22 Issue 26

Current Pharmaceutical Design publishes timely in-depth reviews and research articles from leading pharmaceutical researchers in the field, covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area guest edited by an acknowledged authority in the field.

Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

Articles from the journal Current Pharmaceutical Design , 22 Issue 26

• Editorial (Thematic Issue: Current and Perspective Therapeutic Strategies for Alzheimer’s Disease)
• Protein Amyloidogenesis Investigated by Small Angle Scattering
• AFM-Based Single Molecule Techniques: Unraveling the Amyloid Pathogenic Species
• Heterocyclic Scaffolds for the Treatment of Alzheimer’s Disease
• Metal Ions and Metal Complexes in Alzheimer’s Disease
• Essential Oils and Pure Volatile Compounds as Potential Drugs in Alzheimer’s Disease Therapy: An Updated Review of the Literature
• Therapeutic Approaches Targeting Pathological Tau Aggregates
• Alzheimer’s Disease and Molecular Chaperones: Current Knowledge and the Future of Chaperonotherapy
• The Impact of Small Heat Shock Proteins (HspBs) in Alzheimer’s and Other Neurological Diseases
• Non-Demented Individuals with Alzheimer’s Disease Neuropathology: Resistance to Cognitive Decline May Reveal New Treatment Strategies
• The Potential Use of Piglets as Human Pediatric Surrogate for Preclinical Pharmacokinetic and Pharmacodynamic Drug Testing
• Macrocyclic Compounds: Emerging Opportunities for Current Drug Discovery

For details on the articles, please visit this link :: http://bit.ly/2bQsrvs

courtesy by : Bentham Insight

Read More