114 results match your criteria Amyloidosis Beta2M Dialysis Related


Beta-2 microglobulin and all-cause mortality in the era of high-flux hemodialysis: results from the Dialysis Outcomes and Practice Patterns Study.

Clin Kidney J 2021 May 27;14(5):1436-1442. Epub 2020 Oct 27.

Division of Nephrology, Michael's Hospital, University of Toronto, Toronto, ON, Canada.

Background: Beta-2 microglobulin (β2M) accumulates in hemodialysis (HD) patients, but its consequences are controversial, particularly in the current era of high-flux dialyzers. High-flux HD treatment improves β2M removal, yet β2M and other middle molecules may still contribute to adverse events. We investigated patient factors associated with serum β2M, evaluated trends in β2M levels and in hospitalizations due to dialysis-related amyloidosis (DRA), and estimated the effect of β2M on mortality. Read More

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Enhanced accessibility and hydrophobicity of amyloidogenic intermediates of the β2-microglobulin D76N mutant revealed by high-pressure experiments.

J Biol Chem 2021 Jan 25:100333. Epub 2021 Jan 25.

Department of Biotechnology, Faculty of Biology-oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan.

β2-Microglobulin (β2m) is the causative protein of dialysis-related amyloidosis. Its unfolding mainly proceeds along the pathway of N →U ⇄ U, whereas refolding follows the U → I (→N) →N pathway, in which N, I, and U are the native, intermediate, and unfolded states, respectively, with the Pro32 peptidyl-prolyl bond in cis or trans conformation as indicated by the subscript. It is noted that the I state is a putative amyloidogenic precursor state. Read More

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January 2021

Modulation of Amyloidogenic Protein Self-Assembly Using Tethered Small Molecules.

J Am Chem Soc 2020 12 30;142(49):20845-20854. Epub 2020 Nov 30.

Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom.

Protein-protein interactions (PPIs) are involved in many of life's essential biological functions yet are also an underlying cause of several human diseases, including amyloidosis. The modulation of PPIs presents opportunities to gain mechanistic insights into amyloid assembly, particularly through the use of methods which can trap specific intermediates for detailed study. Such information can also provide a starting point for drug discovery. Read More

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December 2020

The role of the I-state in D76N β-microglobulin amyloid assembly: A crucial intermediate or an innocuous bystander?

J Biol Chem 2020 08 13;295(35):12474-12484. Epub 2020 Jul 13.

Astbury Centre for Structural Molecular Biology, School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom

The D76N variant of human β-microglobulin (βm) is the causative agent of a hereditary amyloid disease. Interestingly, D76N-associated amyloidosis has a distinctive pathology compared with aggregation of WT-βm, which occurs in dialysis-related amyloidosis. A folding intermediate of WT-βm, known as the I-state, which contains a nonnative Pro-32, has been shown to be a key precursor of WT-βm aggregation However, how a single amino acid substitution enhances the rate of aggregation of D76N-βm and gives rise to a different amyloid disease remained unclear. Read More

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Nanobody-Based high-performance immunosorbent for selective beta 2-microglobulin purification from blood.

Acta Biomater 2020 04 22;107:232-241. Epub 2020 Feb 22.

Liaoning Key Laboratory of Molecular Recognition and imaging, School of Bioengineering, Dalian University of Technology, No. 2 Linggong Road, Dalian, Liaoning, 116023, PR China. Electronic address:

Removing β2-microglobulin (β2M) from blood circulation is considered to be the most effective method to delay the occurrence of dialysis-related amyloidosis (DRA). The ideal extracorporeal β2M removal system should be cost-effective, highly specific and having a high capacity. However, the traditional technologies based on size exclusion do not have an adequate specificity, and alternative immunosorbents have limited applications due to low capacity and their high cost. Read More

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Chronic intestinal pseudo-obstruction due to β2microglobulin-amyloidosis in a patient on high-flux haemodialysis.

BMJ Case Rep 2020 Jan 23;13(1). Epub 2020 Jan 23.

Nephrology, Jan Yperman Hospital, Ieper, Belgium.

Dialysis-related amyloidosis (DRA) or β2microglobulin (β2m)-amyloidosis is a disorder caused by the inability to clear a protein called β2m in patients with chronic kidney disease. It results in deposition of β2m as amyloid fibrils, most commonly in bones and joints. Infrequently, visceral organs may be involved. Read More

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January 2020

Collagen I Weakly Interacts with the β-Sheets of β-Microglobulin and Enhances Conformational Exchange To Induce Amyloid Formation.

J Am Chem Soc 2020 01 8;142(3):1321-1331. Epub 2020 Jan 8.

Department of Chemistry and Chemical Biology , Rutgers University , Piscataway , New Jersey 08854 , United States.

Amyloidogenesis is significant in both protein function and pathology. Amyloid formation of folded, globular proteins is commonly initiated by partial or complete unfolding. However, how this unfolding event is triggered for proteins that are otherwise stable in their native environments is not well understood. Read More

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January 2020

Amyloid Formation under Complicated Conditions in Which β-Microglobulin Coexists with Its Proteolytic Fragments.

Biochemistry 2019 12 20;58(49):4925-4934. Epub 2019 Nov 20.

Institute for Protein Research , Osaka University , Yamadaoka 3-2 , Suita , Osaka 565-0871 , Japan.

Amyloid formation in vivo occurs under complicated conditions in which various amyloidogenic and non-amyloidogenic components coexist, often under crowding. Controversy surrounds the role of additional components under complicated conditions. They have been suggested to accelerate amyloid formation because molecular crowding or interactions with additives increase effective concentrations and, thus, break the supersaturation of amyloidogenic proteins. Read More

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December 2019

Structural Heterogeneity in the Preamyloid Oligomers of β-2-Microglobulin.

J Mol Biol 2020 01 9;432(2):396-409. Epub 2019 Nov 9.

Department of Chemistry, University of Massachusetts, Amherst, MA 01003, United States. Electronic address:

In dialysis patients, the protein β2-microglobulin (β2m) forms amyloid fibrils in a condition known as dialysis-related amyloidosis. To understand the early stages of the amyloid assembly process, we have used native electrospray ionization (ESI) together with ion mobility mass spectrometry (IM-MS) to study soluble preamyloid oligomers. ESI-IM-MS reveals the presence of multiple conformers for the dimer, tetramer, and hexamer that precede the Cu(II)-induced amyloid assembly process, results which are distinct from β2m oligomers formed at low pH. Read More

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January 2020

Structural mapping of oligomeric intermediates in an amyloid assembly pathway.

Elife 2019 09 25;8. Epub 2019 Sep 25.

The Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, United Kingdom.

Transient oligomers are commonly formed in the early stages of amyloid assembly. Determining the structure(s) of these species and defining their role(s) in assembly is key to devising new routes to control disease. Here, using a combination of chemical kinetics, NMR spectroscopy and other biophysical methods, we identify and structurally characterize the oligomers required for amyloid assembly of the protein ΔN6, a truncation variant of human β-microglobulin (βm) found in amyloid deposits in the joints of patients with dialysis-related amyloidosis. Read More

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September 2019

Loosening of Side-Chain Packing Associated with Perturbations in Peripheral Dynamics Induced by the D76N Mutation of β-Microglobulin Revealed by Pressure-NMR and Molecular Dynamic Simulations.

Biomolecules 2019 09 16;9(9). Epub 2019 Sep 16.

High Pressure Protein Research Center, Institute of Advanced Technology, Kindai University, 930 Nishimitani, Kinokawa, Wakayama 649-6493, Japan.

β-Microglobulin (βm) is the causative protein of dialysis-related amyloidosis, and its D76N variant is less stable and more prone to aggregation. Since their crystal structures are indistinguishable from each other, enhanced amyloidogenicity induced by the mutation may be attributed to changes in the structural dynamics of the molecule. We examined pressure and mutation effects on the βm molecule by NMR and MD simulations, and found that the mutation induced the loosening of the inter-sheet packing of βm, which is relevant to destabilization and subsequent amyloidogenicity. Read More

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September 2019

-guided identification of potential inhibitors against βm aggregation in dialysis-related amyloidosis.

J Biomol Struct Dyn 2020 Aug 27;38(13):3927-3941. Epub 2019 Sep 27.

School of Chemistry and Biochemistry, Thapar Institute of Engineering & Technology, Patiala, Punjab, India.

In dialysis-related amyloidosis (DRA), misfolding of β-microglobulin (βm) leads to amyloid fibril deposition mainly in the skeletal joints seriously affecting their functionality. The identification and characterization of small-molecules that bind βm and possibly inhibit its aggregation remain unexplored. In the present study, a ligand-based virtual screening approach and molecular dynamics (MD) simulations were employed to explore potent small-molecule inhibitors against βm aggregation. Read More

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Heating during agitation of β-microglobulin reveals that supersaturation breakdown is required for amyloid fibril formation at neutral pH.

J Biol Chem 2019 10 8;294(43):15826-15835. Epub 2019 Sep 8.

Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan

Amyloidosis-associated amyloid fibrils are formed by denatured proteins when supersaturation of denatured proteins is broken. β-Microglobulin (β2m) forms amyloid fibrils and causes dialysis-related amyloidosis in patients receiving long-term hemodialysis. Although amyloid fibrils of β2m in patients are observed at neutral pH, formation of β2m amyloids has been difficult to discern at neutral pH because of the amyloid-resistant native structure. Read More

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October 2019

Biochemical and biophysical comparison of human and mouse beta-2 microglobulin reveals the molecular determinants of low amyloid propensity.

FEBS J 2020 02 28;287(3):546-560. Epub 2019 Aug 28.

Dipartimento di Bioscienze, Università degli Studi di Milano, Italy.

The molecular bases of amyloid aggregation propensity are still poorly understood, especially for proteins that display a stable folded native structure. A prototypic example is human beta-2 microglobulin (β2m), which, when accumulated in patients, gives rise to dialysis-related amyloidosis. Interestingly, although the physiologic concentration of β2m in mice is five times higher than that found in human patients, no amyloid deposits are observed in mice. Read More

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February 2020

The Early Phase of β2m Aggregation: An Integrative Computational Study Framed on the D76N Mutant and the ΔN6 Variant.

Biomolecules 2019 08 14;9(8). Epub 2019 Aug 14.

BioISI-Biosystems & Integrative Sciences Institute and Departamento de Física, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal.

Human β2-microglobulin (b2m) protein is classically associated with dialysis-related amyloidosis (DRA). Recently, the single point mutant D76N was identified as the causative agent of a hereditary systemic amyloidosis affecting visceral organs. To get insight into the early stage of the β2m aggregation mechanism, we used molecular simulations to perform an in depth comparative analysis of the dimerization phase of the D76N mutant and the ΔN6 variant, a cleaved form lacking the first six N-terminal residues, which is a major component of ex vivo amyloid plaques from DRA patients. Read More

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Possible mechanisms of polyphosphate-induced amyloid fibril formation of β-microglobulin.

Proc Natl Acad Sci U S A 2019 06 10;116(26):12833-12838. Epub 2019 Jun 10.

Institute for Protein Research, Osaka University, Suita, 565-0871 Osaka, Japan;

Polyphosphate (polyP), which is found in various microorganisms and human cells, is an anionic biopolymer consisting of inorganic phosphates linked by high-energy phosphate bonds. Previous studies revealed that polyPs strongly promoted the amyloid formation of several amyloidogenic proteins; however, the mechanism of polyP-induced amyloid formation remains unclear. In the present study using β-microglobulin (β2m), a protein responsible for dialysis-related amyloidosis, we investigated amyloid formation in the presence of various chain lengths of polyPs at different concentrations under both acidic (pH 2. Read More

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Investigating the Molecular Basis of the Aggregation Propensity of the Pathological D76N Mutant of Beta-2 Microglobulin: Role of the Denatured State.

Int J Mol Sci 2019 Jan 18;20(2). Epub 2019 Jan 18.

Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Scienze Biochimiche "A. Rossi Fanelli" and Istituto di Biologia e Patologia Molecolari del CNR, Sapienza Università di Roma, 00185 Rome, Italy.

Beta-2 microglobulin (β2m) is a protein responsible for a pathologic condition, known as dialysis-related amyloidosis (DRA), caused by its aggregation and subsequent amyloid formation. A naturally occurring mutation of β2m, D76N, presents a higher amyloidogenic propensity compared to the wild type counterpart. Since the three-dimensional structure of the protein is essentially unaffected by the mutation, the increased aggregation propensity of D76N has been generally ascribed to its lower thermodynamic stability and increased dynamics. Read More

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January 2019

Conformational Properties Relevant to the Amyloidogenicity of β-Microglobulin Analyzed Using Pressure- and Salt-Dependent Chemical Shift Data.

J Phys Chem B 2019 01 15;123(4):836-844. Epub 2019 Jan 15.

Kyoto Prefectural University of Medicine , 465 Kajii-cho , Kamigyo-ku, Kyoto 602-8566 , Japan.

β-Microglobulin (βm) is associated with dialysis-related amyloidosis. In vitro experiments have shown that βm forms amyloid fibrils at acidic pHs in the presence of moderate concentrations of salt. Previous studies suggested that acid-denatured βm has a hydrophobic residual structure, and the exposure of the hydrophobic residues enhances the association with seeds or other βm monomers. Read More

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January 2019

The structure of a β-microglobulin fibril suggests a molecular basis for its amyloid polymorphism.

Nat Commun 2018 10 30;9(1):4517. Epub 2018 Oct 30.

Astbury Centre for Structural Molecular Biology, School of Molecular & Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.

All amyloid fibrils contain a cross-β fold. How this structure differs in fibrils formed from proteins associated with different diseases remains unclear. Here, we combine cryo-EM and MAS-NMR to determine the structure of an amyloid fibril formed in vitro from β-microglobulin (βm), the culprit protein of dialysis-related amyloidosis. Read More

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October 2018

The interaction of β2-microglobulin with gold nanoparticles: impact of coating, charge and size.

J Mater Chem B 2018 Oct 6;6(37):5964-5974. Epub 2018 Sep 6.

DAME, Università di Udine, P.le Kolbe 4, 33100 Udine, Italy.

Gold nanoparticles (AuNPs) have been proved to be ideal scaffolds to build nanodevices whose performance can be tuned by changing their coating. In particular, the interaction of AuNPs with proteins was revealed to be highly dependent on the physico-chemical properties of the gold cluster protecting monolayer. In this work we studied the behavior of three different alkanethiolate-coated AuNPs (AT-AuNPs) when they are incubated with a model amyloidogenic protein, β2-microglobulin (β2m), whose clinical relevance in dialysis-related amyloidosis (DRA) and structural properties are well known. Read More

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October 2018

Tendon thickening in dialysis-related joint arthritis is due to amyloid deposits at the surface of the tendon.

Joint Bone Spine 2019 03 19;86(2):233-238. Epub 2018 Sep 19.

Department of rheumatology, hôpital Lariboisière, 75010 Paris, France; University Paris 7, 75013 Paris, France. Electronic address:

Objectives: Beta-2-microglobulin (β2M) dialysis-related amyloidosis (DRA), a disabiliting joint disease, has been initially reported in patients under long-term dialysis. The incidence and prevalence has significantly decreased with the improvement in dialysis techniques. Here, we attempted to clarify the clinical and MRI features to improve the diagnosis. Read More

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Structural Features of Amyloid Fibrils Formed from the Full-Length and Truncated Forms of Beta-2-Microglobulin Probed by Fluorescent Dye Thioflavin T.

Int J Mol Sci 2018 Sep 14;19(9). Epub 2018 Sep 14.

Laboratory of Structural Dynamics, Stability and Folding of Proteins, Institute of Cytology of the Russian Academy of Science, Tikhoretsky ave. 4, St. Petersburg 194064, Russia.

The persistence of high concentrations of beta-2-microglobulin (β2M) in the blood of patients with acute renal failure leads to the development of the dialysis-related amyloidosis. This disease manifests in the deposition of amyloid fibrils formed from the various forms of β2M in the tissues and biological fluids of patients. In this paper, the amyloid fibrils formed from the full-length β2M (β2m) and its variants that lack the 6 and 10 N-terminal amino acids of the protein polypeptide chain (ΔN6β2m and ΔN10β2m, respectively) were probed by using the fluorescent dye thioflavin T (ThT). Read More

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September 2018

Aggregation-phase diagrams of β-microglobulin reveal temperature and salt effects on competitive formation of amyloids amorphous aggregates.

J Biol Chem 2018 09 3;293(38):14775-14785. Epub 2018 Aug 3.

From the Institute for Protein Research, Osaka University, Osaka 565-0871, Japan,

Several serious diseases are associated with crystal-like amyloid fibrils or glass-like amorphous aggregates of denatured proteins. However, protein aggregation involving both types of aggregates has not yet been elucidated in much detail. Using a protein associated with dialysis-related amyloidosis, β-microglobulin (β2m), we previously demonstrated that amyloid fibrils and amorphous aggregates form competitively depending on salt (NaCl) concentration. Read More

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September 2018

Hemodialysis-related amyloidosis: Is it still relevant?

Semin Dial 2018 11 12;31(6):612-618. Epub 2018 Jun 12.

Department of Nephrology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Accumulation of amyloid fibrils from β2-microglobulin (β2M) was first recognized as a characteristic osteoarticular complication in long-term hemodialysis (HD) patients and called "HD-related amyloidosis" (HRA). However, this syndrome can also be observed in end-stage renal diseases (ESRD) patients undergoing peritoneal dialysis, and even in patients with chronic renal failure before the initiation of dialytic therapy, suggesting that HD is not a direct cause but that accumulation of β2M or some β2M-associated molecules in the body is a common pathogenesis. Currently the term "dialysis-related amyloidosis" (DRA) is widely used for β2M-amyloid (Aβ2M) amyloidosis associated with ESRD, although DRA patients consist mostly of those undergoing long-term HD. Read More

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November 2018

The unresolved problem of beta-2 microglobulin amyloid deposits in the intervertebral discs of long-term dialysis patients.

J Orthop Surg Res 2017 Dec 21;12(1):194. Epub 2017 Dec 21.

Department of Orthopaedic Surgery, Spine Division, Bone and Joint Research Center, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.

Background: Dialysis-related destructive spondyloarthropathy caused by beta-2 microglobulin (β2M) amyloid deposits in intervertebral discs is a major burden for patients undergoing long-term dialysis. This study aimed to quantify the presence of β2M amyloid deposits in the intervertebral disc tissue of such patients and analyze whether there was a significant correlation between β2M accumulation and the duration of dialysis.

Methods: Two groups of patients who had undergone surgery for degenerative spinal pathologies were selected: the dialysis group (n = 29) with long-term dialysis and the control group (n = 10) with no renal impairment. Read More

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December 2017

Assessing the effect of D59P mutation in the DE loop region in amyloid aggregation propensity of β2-microglobulin: A molecular dynamics simulation study.

J Cell Biochem 2018 01 31;119(1):782-792. Epub 2017 Jul 31.

Department of Chemistry, School of Basic and Applied Sciences, Sri Guru Granth Sahib World University, Punjab, India.

Dialysis-related amyloidosis (DRA) is a severe condition characterized by the accumulation of amyloidogenic β2-microglobulin (β2m) protein around skeletal joints and bones. The recent studies highlighted a critical role of the DE loop region for β2m stability and amyloid aggregation propensity. Despite significant efforts, the molecular mechanism of enhanced aggregation due to D59P mutation in the DE loop region remain elusive. Read More

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January 2018

[LEVEL AND OXIDATION OF BETA 2-MICROGLOBULIN IN HEMODIALYSIS PATIENTS TREATED WITH INTRAVENOUS IRON DURING DIALYSIS WITH HIGH-FLUX COMPARED TO LOW-FLUX DIALYZERS].

Harefuah 2017 May;156(5):289-293

Nephrology Department, Galilee Medical Center, Nahariya, Israel.

Introduction: Serum levels of β2-microglobulin (b2M) are significantly higher in patients with end stage renal failure undergoing hemodialysis (HD) and its accumulation accelerates Dialysis Related Amyloidosis (DRA). In HD patients low-flux dialysis, intravenous (IV) iron (administered for the treatment of anemia) affects ß2M removal during dialysis. IV iron also affects the oxidation of plasma proteins, including b2M. Read More

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Small molecule-mediated inhibition of β-2-microglobulin-based amyloid fibril formation.

J Biol Chem 2017 06 3;292(25):10630-10638. Epub 2017 May 3.

From the Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003

In dialysis patients, β-2 microglobulin (β2m) can aggregate and eventually form amyloid fibrils in a condition known as dialysis-related amyloidosis, which deleteriously affects joint and bone function. Recently, several small molecules have been identified as potential inhibitors of β2m amyloid formation Here we investigated whether these molecules are more broadly applicable inhibitors of β2m amyloid formation by studying their effect on Cu(II)-induced β2m amyloid formation. Using a variety of biophysical techniques, we also examined their inhibitory mechanisms. Read More

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Molecular insights into the inhibitory mechanism of rifamycin SV against β-microglobulin aggregation: A molecular dynamics simulation study.

Int J Biol Macromol 2017 Sep 25;102:1025-1034. Epub 2017 Apr 25.

Department of Chemistry, School of Basic and Applied Sciences, Sri Guru Granth Sahib World University, Fatehgarh Sahib 140406, Punjab, India. Electronic address:

Dialysis-related amyloidosis (DRA) is a severe condition characterized by the accumulation of amyloidogenic β-microglobulin (βm) protein around skeletal joints and bones. The small molecules that modulate βm aggregation have been identified in vitro, however, the underlying inhibitory mechanism remain elusive. In the present study, molecular docking and molecular dynamics (MD) simulations were performed to elucidate the inhibitory mechanism of an antibiotic, rifamycin SV (C) reported for its in vitro anti-aggregation activity against βm. Read More

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September 2017