Lysozyme amyloid: evidence for the W64R variant by proteomics in the absence of the wild type protein

Moura, Alexandra; Nocerino, Paola; Gilbertson, Janet A.; Rendell, Nigel B.; Mangione, Palma; Verona, Guglielmo; Rowczenio, Dorota; Gillmore, Julian D.; Taylor, Graham W.; Bellotti, Vittorio; Canetti, Diana

doi:10.1080/13506129.2020.1720637

Cited by 6 publications

(6 citation statements)

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“…Four AL-λ patients expressed high abundance λ subtype proteins. The deposited LC variable region (LCV) is clonotypic and unique to each patient, and thought to be the primary pathogenic driver of the disease [ 28 ]. Maybe it can explain the indolent/localized nature of this disease with MS results.…”

Section: Discussionmentioning

confidence: 99%

A Pilot Study of Rare Renal Amyloidosis Based on FFPE Proteomics

Meng

Xia

et al. 2021

Molecules

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Renal amyloidosis typically manifests albuminuria, nephrotic-range proteinuria, and ultimately progresses to end-stage renal failure if diagnosed late. Different types of renal amyloidosis have completely different treatments and outcomes. Therefore, amyloidosis typing is essential for disease prognosis, genetic counseling and treatment. Thirty-six distinct proteins currently known to cause amyloidosis that have been described as amyloidogenic precursors, immunohistochemistry (IHC) or immunofluorescence (IF), can be challenging for amyloidosis typing especially in rare or hereditary amyloidosis in clinical practice. We made a pilot study that optimized the proteomics pre-processing procedures for trace renal amyloidosis formalin-fixed paraffin-embedded (FFPE) tissue samples, combined with statistical and bioinformatics analysis to screen out the amyloidosis-related proteins to accurately type or subtype renal amyloidosis in order to achieve individual treatment. A sensitive, specific and reliable FFPE-based proteomics analysis for trace sample manipulation was developed for amyloidosis typing. Our results not only underlined the great promise of traditional proteomics and bioinformatics analysis using FFPE tissues for amyloidosis typing, but also proved that retrospective diagnosis and analysis of previous cases laid a solid foundation for personalized treatment.

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Section: Discussionmentioning

confidence: 99%

A Pilot Study of Rare Renal Amyloidosis Based on FFPE Proteomics

Meng

Xia

et al. 2021

Molecules

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“…5 Lysozyme amyloidosis (ALys) is one of the rarest types of systemic amyloidosis. 6 It is a hereditary, autosomal dominant disease that is associated with a single point mutation in the lysozyme gene. To date, 10 amyloid point mutations have been reported.…”

Section: Introductionmentioning

confidence: 99%

“…To date, 10 amyloid point mutations have been reported. 6 ALys is considered a slow-moving disease in early adult life with a median survival rate of approximately 18 years, accompanied by life-threatening clinical manifestations, particularly various hemorrhagic complications. 7 Due to the widespread distribution of lysozyme in many organs throughout the body, ALys may cause multiple organ disorders including digestive damage, spontaneous liver rupture, skin-mucosal disease, heart failure, 7 renal dysfunction, 8 repeated pulmonary infectious episodes, and granulomatosis of the bronchi.…”

Section: Introductionmentioning

confidence: 99%

“…Human lysozyme is a bacteriolytic enzyme widely distributed in a variety of tissues and body fluids, including the gastrointestinal tract, kidneys, liver, lymph nodes, spleen, skin, lachrymal, and salivary glands . Lysozyme amyloidosis (ALys) is one of the rarest types of systemic amyloidosis . It is a hereditary, autosomal dominant disease that is associated with a single point mutation in the lysozyme gene.…”

Section: Introductionmentioning

confidence: 99%

“…It is a hereditary, autosomal dominant disease that is associated with a single point mutation in the lysozyme gene. To date, 10 amyloid point mutations have been reported . ALys is considered a slow-moving disease in early adult life with a median survival rate of approximately 18 years, accompanied by life-threatening clinical manifestations, particularly various hemorrhagic complications .…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Lysozyme Amyloid Fibrillation by Silybin Diastereoisomers: The Effects of Stereochemistry

et al. 2021

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Silybin is a flavonoid lignin compound consisting of two diastereomers with nearly equal molar ratios. It has been reported that silybin can effectively inhibit the aggregation of amyloid protein, but the difference between the two silybin diastereomers has been rarely studied. In this work, the inhibitory ability of silybin to hen egg-white lysozyme (HEWL) was demonstrated, and the difference of kinetic parameters of two diastereomers was analyzed. Fluorescence quenching titration was utilized to analyze the binding differences to native HEWL between the diastereomers, and transmission electron microscopy (TEM) was utilized to analyze the characteristics of the surface of various samples. The differences between hydrophobicity and the secondary structure among several HEWL samples were measured by the 8-anilino-1-naphthalene sulfonic (ANS) acid fluorescence probe, Raman spectra, and far-UV circular dichroism. Moreover, the differences in the binding energy of these two diastereomers with HEWL were analyzed by molecular docking. Also, we have investigated the effect of silybin diastereomers on HEWL fibril-induced cytotoxicity in SH-SY5Y cells. Results show that silybin has a certain inhibitory effect on the HEWL fibrillogenesis process, while silybin B (SB) has a more significant inhibitory effect than silybin A (SA), especially at high concentrations. This work provides some insights into the screening of amyloid inhibitors from complicated natural products and indicates that SB has the prospect of further development as an amyloid inhibitor.

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