scholarly journals Investigation into the Role of Macrophages in the Formation and Degradation of β2-Microglobulin Amyloid Fibrils

2007 ◽  
Vol 282 (40) ◽  
pp. 29691-29700 ◽  
Author(s):  
Isobel J. Morten ◽  
Walraj S. Gosal ◽  
Sheena E. Radford ◽  
Eric W. Hewitt
Keyword(s):  
Amyloid Fibrils ◽  
Β2 Microglobulin

scholarly journals The Effect of Octapeptide Repeats on Prion Folding and Misfolding

2021 ◽  
Vol 22 (4) ◽  
pp. 1800
Author(s):  
Kun-Hua Yu ◽  
Mei-Yu Huang ◽  
Yi-Ru Lee ◽  
Yu-Kie Lin ◽  
Hau-Ren Chen ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Age Of Onset ◽  
Prion Diseases ◽  
Critical Role ◽  
Threshold Effect ◽  
Central Feature ◽  
Terminal Domain ◽  
Amyloid Aggregates

Misfolding of prion protein (PrP) into amyloid aggregates is the central feature of prion diseases. PrP has an amyloidogenic C-terminal domain with three α-helices and a flexible tail in the N-terminal domain in which multiple octapeptide repeats are present in most mammals. The role of the octapeptides in prion diseases has previously been underestimated because the octapeptides are not located in the amyloidogenic domain. Correlation between the number of octapeptide repeats and age of onset suggests the critical role of octapeptide repeats in prion diseases. In this study, we have investigated four PrP variants without any octapeptides and with 1, 5 and 8 octapeptide repeats. From the comparison of the protein structure and the thermal stability of these proteins, as well as the characterization of amyloids converted from these PrP variants, we found that octapeptide repeats affect both folding and misfolding of PrP creating amyloid fibrils with distinct structures. Deletion of octapeptides forms fewer twisted fibrils and weakens the cytotoxicity. Insertion of octapeptides enhances the formation of typical silk-like fibrils but it does not increase the cytotoxicity. There might be some threshold effect and increasing the number of peptides beyond a certain limit has no further effect on the cell viability, though the reasons are unclear at this stage. Overall, the results of this study elucidate the molecular mechanism of octapeptides at the onset of prion diseases.

scholarly journals Evaluation of the serum β2 Microglobulin level in patients with systemic lupus erythematosus and its correlation with disease activity

BioMedicine ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 16 ◽  
Author(s):  
Miramir Aghdashi ◽  
Simak Salami ◽  
Ahmad Nezhadisalami
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Statistical Tests ◽  
Systemic Lupus ◽  
Β2 Microglobulin ◽  
Reactive Protein ◽  
Significant Difference ◽  
Control Study

Background: Designation of disease activity is serious for the management of systemic lupus erythematosus (SLE). Serum level of β2 microglobulin (β2M) may be associated with illness activity in SLE disease. Since the role of β2M for assessing of illness activity in SLE is not completely clear, the current study aimed to discern evaluation of β2M in patients with SLE and its correlation with sickness activity. Materials and Methods: In this case-control study, 50 patients with SLE disease and 25 healthy individuals were selected in Imam Khomeini Hospital in central of Urmia. Blood samples were collected safely from patients, serum was removed, and β2M measured using an ELISA method. The results for other parameters including C reactive protein, C3, C4, anti dsDNA and erythrocyte sedimentation rate were obtained from patients’ medical record. Data analyzed using appropriate statistical tests including Mann-Whitney U test, Independent f-test, Kruskal-Wallis, and Spearman used for analysis of data. Results: In the current study, a significant difference was seen between two groups in terms of β2M (p < 0.001). Remarkable correlation was seen between the level of β2M with disease activity (p < 0.001). Furthermore, there are significant relevancy between the level of β2M with 24-hour urine protein, ESR, disease activity score, and CRP (p < 0.05). Conclusion: The results revealed that serum amount of β2M in SLE patients is higher compared to healthy ones, which is significantly correlated to score of illness activity, CRP, and ESR in patients with SLE disease. Hence β2M might be an excellent serological marker helping the prediction of sickness activity and inflammation in SLE patients.

scholarly journals Advanced Glycation End Product-Modified β2-Microglobulin is a Component of Amyloid Fibrils of Primary Localized Cutaneous Nodular Amyloidosis

2002 ◽  
Vol 118 (3) ◽  
pp. 479-484 ◽  
Author(s):  
Norihiro Fujimoto ◽  
Mayumi Yajima ◽  
Yoshihiro Ohnishi ◽  
Shingo Tajima ◽  
Akira Ishibashi ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Advanced Glycation ◽  
Advanced Glycation End Product ◽  
Β2 Microglobulin

Thermal Response with Exothermic Effects of β2-Microglobulin Amyloid Fibrils and Fibrillation

2009 ◽  
Vol 389 (3) ◽  
pp. 584-594 ◽  
Author(s):  
Kenji Sasahara ◽  
Hisashi Yagi ◽  
Hironobu Naiki ◽  
Yuji Goto
Keyword(s):  
Amyloid Fibrils ◽  
Thermal Response ◽  
Β2 Microglobulin

Protein Fibrillar Nanopolymers: Molecular-Level Insights into Their Structural, Physical and Mechanical Properties

2015 ◽  
Vol 10 (03) ◽  
pp. 135-156 ◽  
Author(s):  
Valeriya M. Trusova
Keyword(s):  
Protein Misfolding ◽  
Amyloid Fibrils ◽  
Molecular Level ◽  
Physical And Mechanical Properties ◽  
Present Contribution ◽  
Wide Range ◽  
Generic Class ◽  
Protein Fibril

Amyloid fibrils represent a generic class of mechanically strong and stable biomaterials with extremely advantageous properties. Although amyloids were initially associated only with severe neurological disorders, the role of these structures nowadays is shifting from health debilitating to highly beneficial both in biomedical and technological aspects. Intensive involvement of fibrillar assemblies into the wide range of pathogenic and functional processes strongly necessitate the molecular level characterization of the structural, physical and elastic features of protein nanofibrils. In the present contribution, we made an attempt to highlight the up-to-date progress in the understanding of amyloid properties from the polymer physics standpoint. The fundamental insights into protein fibril behavior are essential not only for development of therapeutic strategies to combat the protein misfolding disorders but also for rational and precise design of novel biodegradable protein-based nanopolymers.

scholarly journals What Can the Kinetics of Amyloid Fibril Formation Tell about Off-pathway Aggregation?

2015 ◽  
Vol 291 (4) ◽  
pp. 2018-2032 ◽  
Author(s):  
Rosa Crespo ◽  
Eva Villar-Alvarez ◽  
Pablo Taboada ◽  
Fernando A. Rocha ◽  
Ana M. Damas ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Pathogenic Role ◽  
Amyloid Deposits ◽  
Amyloid Fibril Formation ◽  
Microscopy Techniques ◽  
Analytical Tools ◽  
Kinetics Of ◽  
Quantitative Importance

Some of the most prevalent neurodegenerative diseases are characterized by the accumulation of amyloid fibrils in organs and tissues. Although the pathogenic role of these fibrils has not been completely established, increasing evidence suggests off-pathway aggregation as a source of toxic/detoxicating deposits that still remains to be targeted. The present work is a step toward the development of off-pathway modulators using the same amyloid-specific dyes as those conventionally employed to screen amyloid inhibitors. We identified a series of kinetic signatures revealing the quantitative importance of off-pathway aggregation relative to amyloid fibrillization; these include non-linear semilog plots of amyloid progress curves, highly variable end point signals, and half-life coordinates weakly influenced by concentration. Molecules that attenuate/intensify the magnitude of these signals are considered promising off-pathway inhibitors/promoters. An illustrative example shows that amyloid deposits of lysozyme are only the tip of an iceberg hiding a crowd of insoluble aggregates. Thoroughly validated using advanced microscopy techniques and complementary measurements of dynamic light scattering, CD, and soluble protein depletion, the new analytical tools are compatible with the high-throughput methods currently employed in drug discovery.

Role of Cation in Enhancing the Conversion of the Alzheimer’s Peptide into Amyloid Fibrils Using Protic Ionic Liquids

2012 ◽  
Vol 65 (11) ◽  
pp. 1502 ◽  
Author(s):  
Natalie Debeljuh ◽  
Swapna Varghese ◽  
Colin J. Barrow ◽  
Nolene Byrne
Keyword(s):  
Ionic Liquid ◽  
Ionic Liquids ◽  
Primary Amine ◽  
Amyloid Fibrils ◽  
Tertiary Amines ◽  
Protic Ionic Liquids ◽  
Protic Ionic Liquid ◽  
The Difference ◽  
The Impact

We report on the impact of changes in the protic ionic liquid (pIL) cation on the fibrilisation kinetics and the conversion of the Aβ 16–22 from monomers to amyloid fibrils. When we compare the use of primary, secondary, and tertiary amines we find that the primary amine results in the greatest conversion into amyloid fibrils. We show that the pIL is directly interacting with the peptide and this likely drives the difference in conversion and kinetics observed.

Multiplex Analysis of Serum Cytokine Levels in Waldenström Macroglobulinemia Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2616-2616
Author(s):  
Sherine F. Elsawa ◽  
Anne J. Novak ◽  
Steven C. Ziesmer ◽  
Thomas E. Witzig ◽  
Vincent Rajkumar ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Elevated Serum ◽  
Fold Increase ◽  
Serum Levels ◽  
Healthy Controls ◽  
Β2 Microglobulin ◽  
Healthy Donors ◽  
Cytokine Levels

Abstract Waldenström macroglobulinemia (WM) is a monoclonal B cell disorder characterized by a circulating monoclonal IgM protein that may lead to serum hyperviscosity in association with an infiltration of lymphoplasmacytic cells into the bone marrow. Although proinflammatory and chemotactic cytokines can profoundly affect tumor cells and the tumor microenvironment, and many cytokines have been shown to have potent therapeutic efficacy in preclinical cancer models, the role of cytokine networks in WM is not fully understood. In this study, we used a high-throughput xMAP multiplex immunobead assay technology (Luminex Corp., Austin, TX) to simultaneously test 30 cytokines, chemokines, angiogenic factors as well as growth factors and soluble receptors in the sera of WM patients and compared them with other B cell malignancies including IgM monoclonal gammopathy of undetermined significance (MGUS), follicular lymphoma, chronic lymphocytic leukemia (CLL) as well as healthy controls. Using a Mann-Whitney U test to analyze the differences between the groups, 15 of the 30 cytokines tested had significantly different levels in WM compared to healthy controls. Of those 15 cytokines, 11 were elevated in WM patients and 4 were decreased. Cytokines were grouped into 3 groups; those with &lt; 2-fold difference, 2–8 fold difference and those having &gt; 8-fold difference in their cytokine levels compared to healthy donors. There was a greater than 8-fold increase in the serum levels of Rantes, G-CSF and IL-2R (p&lt;0.0001) in WM patients. Furthermore, 3 cytokines had between 2–8-fold increase in WM patients including IL-4 (p&lt;0.0001), IL-6 (p&lt;0.0019) and IP-10 (p&lt;0.0006). Five cytokines had statistically elevated levels in WM patients compared to healthy controls, however the fold increase was &lt; 2 including HGF (p&lt;0.0185), IL-10 (p&lt;0.0002), MIP-1α (P&lt;0.0484), IL-2 (P&lt;0.0130) and IL-12 (P&lt;0.0155). Of the cytokines that had significantly lower levels in the sera of WM patients, IL-8 (p&lt;0.0001) and EGF (p&lt;0.0001) were &gt; 8-fold decreased, MCP-1 (p&lt;0.0001) was 2–8 fold lower and Eotaxin (p&lt;0.0004) was &lt; 2-fold lower in WM patients. All of the cytokines that had the greatest fold difference (&gt; 8-fold) in WM patients compared to healthy donors also differed significantly from the MGUS patients. Rantes, G-CSF, IL-2R and EGF had significantly different levels compared to other B cell malignancies. We tested for a correlation between the cytokines that had &gt; 2-fold difference between the WM group and control group with clinical features of the disease and found the cytokines IL-6 and IL-2R had a significant correlation with β2-microglobulin levels (p&lt;0.01). We analyzed cytokine levels in the bone marrow plasma of the same patients and found that high levels of IL-2R in the bone marrow microenvironment significantly correlated with anemia and elevated serum β2-microglobulin (p&lt;0.01). In conclusion, we have simultaneously analyzed sera from WM patients for 30 cytokines and found the most significantly elevated cytokines are Rantes, G-CSF and IL-2R and the most significantly downregulated cytokines are IL-8 and EGF. Furthermore, we found that elevated serum levels of IL-6 and IL-2R correlated with β2-microglobulin levels, a measure of disease activity. Further analysis of the biological role of these cytokines in WM may offer insight into disease pathogenesis and provide a basis for novel targeted therapies.

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