The pathogenesis of Parkinson's disease that is the second most common neurodegenerative disease is associated with formation of different aggregates of α-synuclein (ASN), namely oligomers and amyloid fibrils. Current research is aimed on the design of fluorescent dyes for the detection of oligomeric aggregates, which are considered to be toxic and morbific spices. Fluorescent properties of series of benzothiazole trimethine and pentamethine cyanines were characterized in free state and in presence of monomeric, oligomeric and fibrilar ASN. The dyes with wide aromatic systems and bulky phenyl and alkyl substituents that are potentially able to interact with hydrophobic regions of oligomeric aggregates were selected for the studies. For majority of studied dyes noticeable changes in fluorescence characteristics were shown in the presence of fibrillar or oligomeric ASN, while the dyes slightly responded on the presence of monomeric protein. For pentamethine cyanine SL-631 and trimethine cyanine SH-299 certain specificity to oligomeric aggregates over fibrils was observed. Using these dyes at 10(-6) M concentration permits the detection of oligomeric ASN in the concentrations range of at least 0.2-2 microM. Pentamethine cyanine SL-631 is proposed as dye for fluorescent detection of oligomeric aggregates of ASN, while trimethine cyanine SH-299 is shown to be a sensitive probe both on oligomeric and fibrillar ASN. It is proposed that wide aromatic system of SL-631 pentamethine dye molecule could better fix on the less dense and structured oligomeric formation, while less bulky and more "crescent-shape" molecule of trimethine dye SH-299 could easier enter into the groove of beta-pleated structure.
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http://dx.doi.org/10.1007/s10895-012-1081-x | DOI Listing |
RSC Chem Biol
December 2024
SSPC - The Science Foundation Ireland Research Centre for Pharmaceuticals, Department of Chemical Sciences, Bernal Institute, University of Limerick Limerick Ireland
Small, stable biomedicines, like peptides and hormones, are already available on the market as spray dried formulations, however large biomolecules like antibodies and therapeutic enzymes continue to pose stability issues during the process. Stresses during solid-state formation are a barrier to formulation of large biotherapeutics as dry powders. Here, we explore an alternative avenue to protein stabilisation during the spray drying process, moving away from the use of excipients.
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German Center for Neurodegenerative Diseases (LMU), Klinikum, Germany.
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View Article and Find Full Text PDFCell Rep
December 2024
Laboratory for Nutritional Biology, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo 650-0047, Japan; Laboratory of Molecular Cell Biology and Development, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address:
An excessive immune response damages organs, yet its molecular mechanism is incompletely understood. Here, we screened a factor mediating organ damage upon genetic activation of the innate immune pathway using Drosophila renal tubules. We found that an antimicrobial peptide, Attacin-D (AttD), causes organ damage upon immune deficiency (Imd) pathway activation in the Malpighian tubules.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
South China Advanced Institute for Soft Matter Science and Technology, School of Emergent Soft Matter, South China University of Technology, Guangzhou, 510640, China.
Cross-β structures are crucial in driving protein folding and aggregation. However, due to their strong aggregating tendency, the precise control of the self-assembly of β-sheet-forming peptides remains a challenge. We propose a molecular geometry strategy to study and control the self-assembly of cross-β structures.
View Article and Find Full Text PDFJ Rheum Dis
January 2025
Division of Rheumatology, Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea.
Gout is the most common inflammatory arthritis in adults, associated with hyperuricemia and the chronic deposition of monosodium urate (MSU) crystals. Hyperuricemia results from increased production of uric acid and decreased excretion by the kidneys and intestines. Urate excretion is regulated by a group of urate transporters, and decreased renal or intestinal excretion is the primary mechanism of hyperuricemia in most people.
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