Recent studies have shown that bacterial nucleoid-associated proteins (NAPs) can bind to DNA and result in altered structural organization and bridging interactions. Under spontaneous self-assembly, NAPs may also form anisotropic amyloid fibers, whose effects are still more significant on DNA dynamics. To test this hypothesis, microrheology experiments on dispersions of DNA associated with the amyloid terminal domain (CTR) of the bacterial protein Hfq were performed using magnetic rotational spectroscopy (MRS). In this chapter, we survey this microrheology technique based on the remote actuation of magnetic wires embedded in a sample. MRS is interesting as it is easy to implement and does not require complex procedures regarding data treatment. Pertaining to the interaction between DNA and amyloid fibers, it is found that DNA and Hfq-CTR protein dispersions behave like a gel, an outcome that suggests the formation of a network of amyloid fibers cross-linked with the DNA strands. In contrast, the pristine DNA and Hfq-CTR dispersions behave as purely viscous liquids. To broaden the scope of the MRS technique, we include theoretical predictions for the rotation of magnetic wires regarding the generic behaviors of basic rheological models from continuum mechanics, and we list the complex fluids studied by this technique over the past 10 years.
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http://dx.doi.org/10.1007/978-1-0716-2529-3_19 | DOI Listing |
Biophys Rev
December 2024
Amity Institute of Molecular Medicine and Stem Cell Research, Amity University Uttar Pradesh, 201313 Noida, India.
Amyloid fibrils, historically stigmatized due to their association with diseases like Alzheimer's and Parkinson's, are now recognized as a distinct class of functional proteins with extraordinary potential. These highly ordered, cross-β-sheet protein aggregates are found across all domains of life, playing crucial physiological roles. In bacteria, functional amyloids like curli fibers are essential for surface adhesion, biofilm formation, and viral DNA packaging.
View Article and Find Full Text PDFAlzheimers Res Ther
January 2025
School of Optometry, University of Alabama at Birmingham, Birmingham, AL, US.
Background: The potential diagnostic value of plasma amyloidogenic beta residue 42/40 ratio (Aβ42/Aβ40 ratio), neurofilament light (NfL), tau phosphorylated at threonine-181 (p-tau181), and threonine-217 (p-tau217) has been extensively discussed in the literature. We have also previously described the association between retinal biomarkers and preclinical Alzheimer's disease (AD). The goal of this study was to evaluate the association, and a multimodal model of, retinal and plasma biomarkers for detection of preclinical AD.
View Article and Find Full Text PDFBiomedicines
December 2024
Department of Histology, Jagiellonian University Medical College, Kopernika 7, 31-034 Krakow, Poland.
Background: The levels of β-amyloid precursor protein (β-APP), tau protein, and phosphorylation of tau (p-tau) protein were examined by quantitative immunohistochemistry in the spinal cord sections of mice suffering from experimental autoimmune encephalomyelitis (EAE) in the successive phases of the disease: onset, peak, and chronic.
Methods: EAE was induced in C57BL/6 mice by immunization with MOG35-55 peptide. The degree of pathological changes was assessed in cross-sections of the entire spinal cord.
Anal Chem
January 2025
Institut de Recherche en Santé, Environnement et Travail (Irset)─Inserm─EHESP, UMR_S 1085, Université de Rennes, 9 av. du Professeur Léon Bernard, F-35042 Rennes, France.
Amyloidosis is a group of proteinopathies characterized by the systemic or organ-specific deposition of proteins in the form of amyloid fibers. Nearly 40 proteins play a role in these pathologies, and the structures of the associated fibers are beginning to be determined by Cryo-EM. However, the molecular events underlying the process, such as fiber nucleation and elongation, are poorly understood, which impairs developing efficient therapies.
View Article and Find Full Text PDFJ Med Chem
January 2025
Graduate School of Innovative Life Science, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan.
Transthyretin (TTR), a plasma protein, undergoes transformation into amyloid fibers, leading to ATTRv amyloidosis, a disease characterized by organ deposition of TTR amyloid fibrils and subsequent organ failure. Developing compounds that bind and kinetically stabilize TTR is a crucial strategy in the treatment of ATTRv amyloidosis. In this study, we narrowed 651 pesticide-related compounds down to 14 possible TTR binders through in silico screening; subsequent in vitro analysis revealed that 7 of them exhibited amyloid fibril formation inhibition activity.
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