scholarly journals A Brief View of the Surface Membrane Proteins fromTrypanosoma cruzi

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Ángel de la Cruz Pech-Canul ◽  
Victor Monteón ◽  
Rosa-Lidia Solís-Oviedo
Keyword(s):  
Life Cycle ◽  
Membrane Proteins ◽  
South America ◽  
Cell Surface ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Surface Membrane ◽  
Surface Molecules ◽  
The World ◽  
Large Families

Trypanosoma cruziis the causal agent of Chagas’ disease which affects millions of people around the world mostly in Central and South America.T. cruziexpresses a wide variety of proteins on its surface membrane which has an important role in the biology of these parasites. Surface molecules of the parasites are the result of the environment to which the parasites are exposed during their life cycle. Hence,T. cruzidisplays several modifications when they move from one host to another. Due to the complexity of this parasite’s cell surface, this review presents some membrane proteins organized as large families, as they are the most abundant and/or relevant throughout theT. cruzimembrane.

scholarly journals Identification of novel therapeutic targets for histone 3 mutated children’s brain tumour, using unique tumour cell surface proteomic signatures

2021 ◽  
Vol 23 (Supplement_4) ◽  
pp. iv9-iv9
Author(s):  
Anya Snary ◽  
Richard Grundy ◽  
Rob Layfield ◽  
Ruman Rahman ◽  
Farhana Haque
Keyword(s):  
Membrane Proteins ◽  
Cell Membrane ◽  
Cell Surface ◽  
Brain Tumours ◽  
Expression Patterns ◽  
Surface Membrane ◽  
Therapeutic Targets ◽  
Molecular Signature ◽  
Histone 3 ◽  
Cell Membrane Proteins

Abstract Aims Improvements in the treatments for childhood and adolescent brain tumours, High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), have not advanced much and they continue to carry a very poor prognosis. These brain tumours are now defined by mutations affecting histone 3 proteins, indeed 80% of DIPGs harbour histone H3.1 and H3.3 K27M somatic mutations whilst 30% of pHGGs exhibit H3.3 G34R or G34V mutations. We hypothesized that the histone 3 mutant tumours will have distinct mutation specific surfactome (cell membrane proteins) signature. Method We therefore analysed the cell surface proteomics of pHGG and DIPG, in order to identify novel targets for therapy. We have at first isolated the cell membrane fractions from a range of patient cells carrying different histone 3 mutations (G34R, G34V), relative to wild type histone 3. A comparative quantitative mass-spectrometry analyses of these cell surface membrane fractions is then performed. Results The results obtained to date demonstrated unique differential cell membrane expression patterns which correlated to specific mutation type. For example, increased expression of Ras-related proteins Rab-3, Rab-3D is detected only in histone H3.3-G34R mutated cell line in comparison. Conclusion Identification and analyses of these unique cell membrane proteins’ association with specific in H3.3 mutation in pHGG, will help to identify precise mutation specific therapeutic targets, benefiting the patients to receive therapy based on tumour’s molecular signature.

Probing for Trypanosoma cruzi Cell Surface Glycobiomarkers for the Diagnosis and Follow-Up of Chemotherapy of Chagas Disease

2017 ◽  
pp. 195-211
Author(s):  
Nathaniel S. Schocker ◽  
Susana Portillo ◽  
Roger A. Ashmus ◽  
Carlos R. N. Brito ◽  
Igor E. Silva ◽  
...  
Keyword(s):  
Cell Surface ◽  
Trypanosoma Cruzi ◽  
Chagas Disease

scholarly journals A Disintegrin and Metalloproteases (ADAMs) in Cardiovascular, Metabolic and Inflammatory Diseases: Aspects for Theranostic Approaches

2018 ◽  
Vol 118 (07) ◽  
pp. 1167-1175 ◽  
Author(s):  
Emiel van der Vorst ◽  
Christian Weber ◽  
Marjo Donners
Keyword(s):  
Rheumatoid Arthritis ◽  
Growth Factors ◽  
Membrane Proteins ◽  
Cell Surface ◽  
Inflammatory Diseases ◽  
Cell Surface Molecules ◽  
Surface Molecules ◽  
Membrane Bound ◽  
Membrane Bound Enzymes ◽  
Key Questions

AbstractA disintegrin and metalloproteases (ADAMs) are membrane-bound enzymes responsible for the shedding or cleavage of various cell surface molecules, such as adhesion molecules, cytokines/chemokines and growth factors. This shedding can result in the release of soluble proteins that can exert agonistic or antagonistic functions. Additionally, ADAM-mediated cleavage can render these membrane proteins inactive. This review will describe the role and association of ADAMs in various pathologies with a main focus on ADAM10 and ADAM17 in atherosclerosis, including a brief overview of atherosclerosis-related ADAM substrates. Furthermore, ADAMs involvement in other metabolic and inflammatory diseases like diabetes, sepsis, Alzheimer's disease and rheumatoid arthritis will be highlighted. Subsequently, we will briefly discuss an interesting emerging field of research, i.e. the potential implications of ADAM expression in extracellular vesicles. Finally, several ADAM-based therapeutic and diagnostic (theranostic) opportunities will be discussed, while focusing on key questions about the required specificity and selectivity.

scholarly journals The remarkable pioneering contribution of Gaspar Vianna to the study of the neuropathology of Chagas disease

2018 ◽  
Vol 76 (12) ◽  
pp. 853-856
Author(s):  
José Eymard Homem Pittella
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Life Cycle ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Acute Phase ◽  
Central Nervous System Involvement ◽  
System Involvement

ABSTRACT Gaspar Vianna is considered one of the great names in Medicine and Science in Brazil. Yet, little prominence has been given to his studies in Neuropathology. He was the first to describe, in 1911, the histopathology and pathogenesis of chagasic encephalitis in the acute phase of Chagas disease, as well as the intracellular life cycle of Trypanosoma cruzi. Over 100 years have elapsed and Gaspar Vianna's pioneering study remains an example of a meticulous and still up-to-date description of central nervous system involvement in the acute phase of Chagas disease.

scholarly journals Trypanosoma cruzi Phosphomannomutase and Guanosine Diphosphate-Mannose Pyrophosphorylase Ligandability Assessment

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Filip Zmuda ◽  
Sharon M. Shepherd ◽  
Michael A. J. Ferguson ◽  
David W. Gray ◽  
Leah S. Torrie ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Cell Surface ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
De Novo ◽  
Chemical Space ◽  
Nucleotide Sugar ◽  
Content Type ◽  
Life Cycle Stages ◽  
Drug Discovery Program

ABSTRACT Chagas’ disease, which is caused by the Trypanosoma cruzi parasite, has become a global health problem that is currently treated with poorly tolerated drugs that require prolonged dosing. Therefore, there is a clinical need for new therapeutic agents that can mitigate these issues. The phosphomannomutase (PMM) and GDP-mannose pyrophosphorylase (GDP-MP) enzymes form part of the de novo biosynthetic pathway to the nucleotide sugar GDP-mannose. This nucleotide sugar is used either directly, or indirectly via the formation of dolichol-phosphomannose, for the assembly of all mannose-containing glycoconjugates. In T. cruzi, mannose-containing glycoconjugates include the cell-surface glycoinositol-phospholipids and the glycosylphosphatidylinositol-anchored mucin-like glycoproteins that dominate the cell surface architectures of all life cycle stages. This makes PMM and GDP-MP potentially attractive targets for a drug discovery program against Chagas’ disease. To assess the ligandability of these enzymes in T. cruzi, we have screened 18,117 structurally diverse compounds exploring drug-like chemical space and 16,845 small polar fragment compounds using an assay interrogating the activities of both PMM and GDP-MP enzymes simultaneously. This resulted in 48 small fragment hits, and on retesting 20 were found to be active against the enzymes. Deconvolution revealed that these were all inhibitors of T. cruzi GDP-MP, with compounds 2 and 3 acting as uncompetitive and competitive inhibitors, respectively. Based on these findings, the T. cruzi PMM and GDP-MP enzymes were deemed not ligandable and poorly ligandable, respectively, using small molecules from conventional drug discovery chemical space. This presents a significant hurdle to exploiting these enzymes as therapeutic targets for Chagas’ disease.

scholarly journals Treatment of Chagas Cardiomyopathy

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Fernando A. Botoni ◽  
Antonio Luiz P. Ribeiro ◽  
Carolina Coimbra Marinho ◽  
Marcia Maria Oliveira Lima ◽  
Maria do Carmo Pereira Nunes ◽  
...  
Keyword(s):  
North America ◽  
South America ◽  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Therapeutic Approach ◽  
Original Description ◽  
Tropical Disease ◽  
Neglected Tropical Disease ◽  
Underdeveloped Countries ◽  
Chagas Cardiomyopathy

Chagas' disease (ChD), caused by the protozoaTrypanosoma cruzi(T. cruzi), was discovered and described by the Brazilian physician Carlos Chagas in 1909. After a century of original description, trypanosomiasis still brings much misery to humanity and is classified as a neglected tropical disease prevalent in underdeveloped countries, particularly in South America. It is an increasing worldwide problem due to the number of cases in endemic areas and the migration of infected subjects to more developed regions, mainly North America and Europe. Despite its importance, chronic chagas cardiomyopathy (CCC) pathophysiology is yet poorly understood, and independently of its social, clinical, and epidemiological importance, the therapeutic approach of CCC is still transposed from the knowledge acquired from other cardiomyopathies. Therefore, the objective of this review is to describe the treatment of Chagas cardiomyopathy with emphasis on its peculiarities.

scholarly journals Cell surface molecules and fibronectin-mediated cell adhesion: effect of proteolytic digestion of membrane proteins.

1982 ◽  
Vol 94 (1) ◽  
pp. 179-186 ◽  
Author(s):  
G Tarone ◽  
G Galetto ◽  
M Prat ◽  
P M Comoglio
Keyword(s):  
Protein Synthesis ◽  
Cell Adhesion ◽  
Membrane Proteins ◽  
Cell Surface ◽  
Rabbit Antiserum ◽  
Proteinase K ◽  
Proteolytic Digestion ◽  
Adhesive Properties ◽  
Surface Molecules ◽  
Protein Nature

Proteases have been used as a tool to investigate the role of surface molecules in fibronectin-mediated cell adhesion. Proteolytic digestion of membrane-proteins by pronase (1 mg/ml for 20 min at 37 degrees C) completely inhibited adhesion of baby hamster kidney (BHK) fibroblasts on fibronectin-coated plastic dishes. Various degrees of inhibition were also obtained after treatment with proteinase K, chymotrypsin, papain, subtilopeptidase A, and thermolysin. Protein synthesis was required to restore the adhesive properties of pronase-treated cells, showing the protein nature of the molecules involved in adhesion to fibronectin. A peculiar feature of these proteins was their resistance to cleavage by trypsin. After prolonged trypsin treatment (1 mg/ml for 20 min at 37 degrees C), cells adhered and spread on fibronectin-coated dishes, even when protein synthesis was inhibited by 4 microM cycloheximide. Under these conditions only three glycoproteins (gp) of molecular weight 130,000, 120,000, and 80,000 were left on the cell surface. These were precipitated by a rabbit antiserum against BHK cells that also inhibited adhesion of trypsin-treated cells. gp120 and gp80 were left at the cell surface after mild pronase digestion (0.2 mg/ml for 20 min at 37 degrees C), under conditions not affecting adhesion. These data suggest that these glycoproteins may be involved in fibronectin-mediated cell adhesion in some yet unknown way.

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