scholarly journals Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

2015 ◽  
Vol 11 ◽  
pp. 659-667 ◽  
Author(s):  
Mathieu L Lepage ◽  
Antoine Mirloup ◽  
Manon Ripoll ◽  
Fabien Stauffert ◽  
Anne Bodlenner ◽  
...  
Keyword(s):  
Protein Misfolding ◽  
Gaucher Disease ◽  
Photophysical Properties ◽  
Genetic Diseases ◽  
Molecular Probes ◽  
Design Synthesis ◽  
Pharmacological Chaperones ◽  
Rare Genetic Diseases ◽  
Photochemical Properties ◽  
Fluorescent Analogues

The synthesis and photophysical properties of the first examples of iminosugar clusters based on a BODIPY or a pyrene core are reported. The tri- and tetravalent systems designed as molecular probes and synthesized by way of Cu(I)-catalysed azide–alkyne cycloadditions are fluorescent analogues of potent pharmacological chaperones/correctors recently reported in the field of Gaucher disease and cystic fibrosis, two rare genetic diseases caused by protein misfolding.

Chemical and pharmacological chaperones as new therapeutic agents

2007 ◽  
Vol 9 (16) ◽  
pp. 1-18 ◽  
Author(s):  
Tip W. Loo ◽  
David M. Clarke
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Misfolding ◽  
Clinical Symptoms ◽  
Genetic Diseases ◽  
Point Mutations ◽  
Therapeutic Agents ◽  
Great Promise ◽  
Functional Protein ◽  
Pharmacological Chaperones ◽  
New Class

Proteins that are exported from the cell, or targeted to the cell surface or other organelles, are synthesised and assembled in the endoplasmic reticulum and then delivered to their destinations. Point mutations – the most common cause of human genetic diseases – can inhibit folding and assembly of the protein in the endoplasmic reticulum. The unstable or partially folded mutant protein does not undergo trafficking and is usually rapidly degraded. A potential therapy for protein misfolding is to correct defective protein folding and trafficking using pharmacological chaperones. Pharmacological chaperones are substrates or modulators that appear to function by directly binding to the partially folded biosynthetic intermediate to stabilise the protein and allow it to complete the folding process to yield a functional protein. Initial clinical studies with pharmacological chaperones have successfully reduced clinical symptoms of disease. Therefore, pharmacological chaperones show great promise as a new class of therapeutic agents that can be specifically tailored for a particular genetic disease.

scholarly journals Considerations for Home-Based Treatment of Fabry Disease in Poland during the COVID-19 Pandemic and Beyond

2021 ◽  
Vol 18 (16) ◽  
pp. 8242
Author(s):  
Michał Nowicki ◽  
Stanisława Bazan-Socha ◽  
Mariusz Kłopotowski ◽  
Beata Błażejewska-Hyżorek ◽  
Mariusz Kusztal ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Genetic Diseases ◽  
Healthcare Providers ◽  
Treatment Programs ◽  
Current Therapy ◽  
Term Care ◽  
Pharmacological Chaperone ◽  
Enzyme Replacement ◽  
Home Based ◽  
Rare Genetic Diseases

Current therapy for Anderson–Fabry disease in Poland includes hospital or clinic-based intravenous enzyme replacement therapy with recombinant agalsidase alpha or beta, or oral pharmacological chaperone therapy with migalastat. Some countries around the world offer such treatment to patients in the comfort of their own homes. The 2020–2021 COVID-19 pandemic has pushed global healthcare providers to evolve their services so as to minimize the risk of COVID-19 exposure to both patients and providers; this has led to advances in telemedicine services and the increasing availability of at-home treatment for various procedures including parenteral drug administration. A total of 80% of surveyed Anderson–Fabry disease patients in Poland would prefer home-based treatment, which would be a safe and convenient alternative to clinic-based treatment if patient selection is based on our proposed algorithm. Our recommendations for home-based treatments appear feasible for the long term care of Anderson–Fabry disease patients during the COVID-19 pandemic and beyond. This may also serve as a basis for home-based treatment programs in other rare and ultra-rare genetic diseases.

scholarly journals Design, Synthesis, and Evaluation of Coumarin-Based Molecular Probes for Imaging of Myelination

2011 ◽  
Vol 54 (7) ◽  
pp. 2331-2340 ◽  
Author(s):  
Changning Wang ◽  
Chunying Wu ◽  
Junqing Zhu ◽  
Robert H. Miller ◽  
Yanming Wang
Keyword(s):  
Molecular Probes ◽  
Design Synthesis

scholarly journals TRIM32 and Malin in Neurological and Neuromuscular Rare Diseases

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 820
Author(s):  
Lorena Kumarasinghe ◽  
Lu Xiong ◽  
Maria Adelaida Garcia-Gimeno ◽  
Elisa Lazzari ◽  
Pascual Sanz ◽  
...  
Keyword(s):  
Common Ancestor ◽  
Genetic Diseases ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Lafora Disease ◽  
C Terminus ◽  
Rare Genetic Diseases ◽  
Tripartite Motif ◽  
Trim Proteins ◽  
Ring E3

Tripartite motif (TRIM) proteins are RING E3 ubiquitin ligases defined by a shared domain structure. Several of them are implicated in rare genetic diseases, and mutations in TRIM32 and TRIM-like malin are associated with Limb-Girdle Muscular Dystrophy R8 and Lafora disease, respectively. These two proteins are evolutionary related, share a common ancestor, and both display NHL repeats at their C-terminus. Here, we revmniew the function of these two related E3 ubiquitin ligases discussing their intrinsic and possible common pathophysiological pathways.

Design, synthesis and photophysical properties of A-D-A-D-A small molecules for photovoltaic application

2015 ◽  
Vol 121 ◽  
pp. 99-108 ◽  
Author(s):  
Weibo Yan ◽  
Qian Zhang ◽  
Qingsong Qin ◽  
Senyun Ye ◽  
Yuanwei Lin ◽  
...  
Keyword(s):  
Small Molecules ◽  
Photophysical Properties ◽  
Design Synthesis ◽  
Photovoltaic Application

scholarly journals High-Throughput Sequencing and Rare Genetic Diseases

2012 ◽  
Vol 3 (5) ◽  
pp. 197-203 ◽  
Author(s):  
P. Makrythanasis ◽  
S.E. Antonarakis
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Genetic Diseases ◽  
Rare Genetic Diseases

Burden of care in families of patients with rare genetic diseases: analysis of a large Italian cohort

2021 ◽  
pp. 104230
Author(s):  
Alex Moretti ◽  
Paola Cianci ◽  
Anita De Paoli ◽  
Francesca Meroni ◽  
Silvia Tajè ◽  
...  
Keyword(s):  
Genetic Diseases ◽  
Burden Of Care ◽  
Rare Genetic Diseases ◽  
Italian Cohort

Ethics and equity in rare disease research and healthcare

2021 ◽  
Author(s):  
Maria Koromina ◽  
Vasileios Fanaras ◽  
Gareth Baynam ◽  
Christina Mitropoulou ◽  
George P Patrinos
Keyword(s):  
Rare Diseases ◽  
Ethical Issues ◽  
Genetic Diseases ◽  
Ethical Framework ◽  
Middle Income ◽  
Next Generation Sequencing Technology ◽  
Ethical Frameworks ◽  
Rare Genetic Diseases ◽  
Conducting Research ◽  
Key Aspects

Rapid advances in next-generation sequencing technology, particularly whole exome sequencing and whole genome sequencing, have greatly affected our understanding of genetic variation underlying rare genetic diseases. Herein, we describe ethical principles of guiding consent and sharing of genomics research data. We also discuss ethical dilemmas in rare diseases research and patient recruitment policies and address bioethical and societal aspects influencing the ethical framework for genetic testing. Moreover, we focus on addressing ethical issues surrounding research in low- and middle-income countries. Overall, this perspective aims to address key aspects and issues for building proper ethical frameworks, when conducting research involving genomics data with a particular emphasis on rare diseases and genetics testing.

scholarly journals Oligonucleotides DNA containing 8-trifluoromethyl-2′-deoxyguanosine for observing Z-DNA structure

2020 ◽  
Author(s):  
Hong-Liang Bao ◽  
Tatsuki Masuzawa ◽  
Takanori Oyoshi ◽  
Yan Xu
Keyword(s):  
Genetic Diseases ◽  
Dna Structure ◽  
2D Nmr ◽  
Living Cells ◽  
Molecular Probes ◽  
Alternative Form ◽  
Left Handed ◽  
Z Dna ◽  
And Function

Abstract Z-DNA is known to be a left-handed alternative form of DNA and has important biological roles as well as being related to cancer and other genetic diseases. It is therefore important to investigate Z-DNA structure and related biological events in living cells. However, the development of molecular probes for the observation of Z-DNA structures inside living cells has not yet been realized. Here, we have succeeded in developing site-specific trifluoromethyl oligonucleotide DNA by incorporation of 8-trifluoromethyl-2′-deoxyguanosine (FG). 2D NMR strongly suggested that FG adopted a syn conformation. Trifluoromethyl oligonucleotides dramatically stabilized Z-DNA, even under physiological salt concentrations. Furthermore, the trifluoromethyl DNA can be used to directly observe Z-form DNA structure and interaction of DNA with proteins in vitro, as well as in living human cells by19F NMR spectroscopy for the first time. These results provide valuable information to allow understanding of the structure and function of Z-DNA.

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