scholarly journals Synergy of the Inhibitory Action of Polyphenols Plus Vitamin C on Amyloid Fibril Formation: Case Study of Human Stefin B

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1471
Author(s):  
Alma Jahić Mujkić ◽  
Magda Tušek Žnidarič ◽  
Selma Berbić ◽  
Eva Žerovnik
Keyword(s):  
Vitamin C ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Missense Mutations ◽  
Progressive Myoclonus Epilepsy ◽  
Amyloid Fibril Formation ◽  
Myoclonus Epilepsy ◽  
Antioxidant Concentration

In order to study how polyphenols and vitamin C (vitC) together affect protein aggregation to amyloid fibrils, we performed similar in vitro studies as before using stefin B as a model and a potentially amyloid-forming protein (it aggregates upon overexpression, under stressful conditions and some progressive myoclonus epilepsy of tape 1—EPM1-missense mutations). In addition to the chosen polyphenol, this time, we added a proven antioxidant concentration of 0.5 mM vitC into the fibrillation mixture and varied concentrations of resveratrol, quercetin, and curcumin. Synergy with vitC was observed with curcumin and quercetin.

Effect of pH and inhibitors on beta-amyloid fibril assembly

1996 ◽  
Vol 54 ◽  
pp. 752-753
Author(s):  
Beverly E. Maleeff ◽  
Timothy K. Hart ◽  
Stephen J. Wood ◽  
Ronald Wetzel
Keyword(s):  
Amyloid Fibril ◽  
Peptide Fragment ◽  
Hydrophobic Peptides ◽  
Amyloid Fibril Formation ◽  
Effects Of Ph ◽  
Severity Of The Disease ◽  
Kinetics Of ◽  
The Brain

Alzheimer's disease is characterized post-mortem in part by abnormal extracellular neuritic plaques found in brain tissue. There appears to be a correlation between the severity of Alzheimer's dementia in vivo and the number of plaques found in particular areas of the brain. These plaques are known to be the deposition sites of fibrils of the protein β-amyloid. It is thought that if the assembly of these plaques could be inhibited, the severity of the disease would be decreased. The peptide fragment Aβ, a precursor of the p-amyloid protein, has a 40 amino acid sequence, and has been shown to be toxic to neuronal cells in culture after an aging process of several days. This toxicity corresponds to the kinetics of in vitro amyloid fibril formation. In this study, we report the biochemical and ultrastructural effects of pH and the inhibitory agent hexadecyl-N-methylpiperidinium (HMP) bromide, one of a class of ionic micellar detergents known to be capable of solubilizing hydrophobic peptides, on the in vitro assembly of the peptide fragment Aβ.

scholarly journals The Ultrastructure of Tissue Damage by Amyloid Fibrils

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4611
Author(s):  
Haruki Koike ◽  
Masahisa Katsuno
Keyword(s):  
Tissue Damage ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Prion Diseases ◽  
Nerve Biopsy ◽  
Al Amyloidosis ◽  
Amyloid Fibril Formation ◽  
Autopsy Specimens ◽  
Fibril Aggregates ◽  
Interfering Rna

Amyloidosis is a group of diseases that includes Alzheimer’s disease, prion diseases, transthyretin (ATTR) amyloidosis, and immunoglobulin light chain (AL) amyloidosis. The mechanism of organ dysfunction resulting from amyloidosis has been a topic of debate. This review focuses on the ultrastructure of tissue damage resulting from amyloid deposition and therapeutic insights based on the pathophysiology of amyloidosis. Studies of nerve biopsy or cardiac autopsy specimens from patients with ATTR and AL amyloidoses show atrophy of cells near amyloid fibril aggregates. In addition to the stress or toxicity attributable to amyloid fibrils themselves, the toxicity of non-fibrillar states of amyloidogenic proteins, particularly oligomers, may also participate in the mechanisms of tissue damage. The obscuration of the basement and cytoplasmic membranes of cells near amyloid fibrils attributable to an affinity of components constituting these membranes to those of amyloid fibrils may also play an important role in tissue damage. Possible major therapeutic strategies based on pathophysiology of amyloidosis consist of the following: 1) reducing or preventing the production of causative proteins; 2) preventing the causative proteins from participating in the process of amyloid fibril formation; and/or 3) eliminating already-deposited amyloid fibrils. As the development of novel disease-modifying therapies such as short interfering RNA, antisense oligonucleotide, and monoclonal antibodies is remarkable, early diagnosis and appropriate selection of treatment is becoming more and more important for patients with amyloidosis.

scholarly journals The amphibian antimicrobial peptide uperin 3.5 is a cross-α/cross-β chameleon functional amyloid

2021 ◽  
Vol 118 (3) ◽  
pp. e2014442118
Author(s):  
Nir Salinas ◽  
Einav Tayeb-Fligelman ◽  
Massimo D. Sammito ◽  
Daniel Bloch ◽  
Raz Jelinek ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Membrane Damage ◽  
Fibril Formation ◽  
Regulation Mechanism ◽  
Bacterial Cells ◽  
Amyloid Fibril Formation ◽  
Β Amyloid ◽  
Β Sheets

Antimicrobial activity is being increasingly linked to amyloid fibril formation, suggesting physiological roles for some human amyloids, which have historically been viewed as strictly pathological agents. This work reports on formation of functional cross-α amyloid fibrils of the amphibian antimicrobial peptide uperin 3.5 at atomic resolution, an architecture initially discovered in the bacterial PSMα3 cytotoxin. The fibrils of uperin 3.5 and PSMα3 comprised antiparallel and parallel helical sheets, respectively, recapitulating properties of β-sheets. Uperin 3.5 demonstrated chameleon properties of a secondary structure switch, forming mostly cross-β fibrils in the absence of lipids. Uperin 3.5 helical fibril formation was largely induced by, and formed on, bacterial cells or membrane mimetics, and led to membrane damage and cell death. These findings suggest a regulation mechanism, which includes storage of inactive peptides as well as environmentally induced activation of uperin 3.5, via chameleon cross-α/β amyloid fibrils.

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.

Cerebrospinal fluid inhibits Alzheimer ?-amyloid fibril formation in vitro

1993 ◽  
Vol 34 (4) ◽  
pp. 631-633 ◽  
Author(s):  
Thomas Wisniewski ◽  
Eduardo Castano ◽  
Jorge Ghiso ◽  
Blas Frangione
Keyword(s):  
Cerebrospinal Fluid ◽  
Amyloid Fibril ◽  
Fibril Formation ◽  
Amyloid Fibril Formation

scholarly journals Antioxidants From the Class of Polyphenols, NAC and Vitamin C Act Differently on Amyloid Fibril Formation by Two Human Cystatins: Stefin B and Cystatin C.

2020 ◽  
Author(s):  
Alma Jahic Mujkic ◽  
Samra Hasanbasic ◽  
Magda Tušek Žnidarič ◽  
Selma Berbic ◽  
Eva Zerovnik
Keyword(s):  
Vitamin C ◽  
Cystatin C ◽  
Amyloid Fibril ◽  
Synergistic Effects ◽  
Fibril Formation ◽  
Homologous Proteins ◽  
Amyloid Fibril Formation ◽  
Transmission Electron ◽  
Amyloid Fibrillation ◽  
Anti Oxidant

We compare the effect on amyloid fibril formation by two homologous proteins from the family of cystatins, human stefin B (stB) and cystatin C (cysC) in presence of 3 polyphenols: curcumin, resveratrol and quercetin and 2 non-phenolic anti-oxidants: vitamin C (VitC) and N-acetyl cystein (NAC). Some of the experimental data have already been presented, here we compare, further discuss and highlight the results. The amyloid fibril formation was followed by ThT fluorescence and transmission electron microscopy. Inhibitory effects on amyloid fibrillation reaction depended on anti-oxidant class and concentration. The fact that different effect of polyphenols was observed with the two cystatins; Cur acted inhibitory on stB but not on cysC fibril formation, could be explained if the 3 polyphenols would not bind to the same binding site in the fibrils core. Other differences are pointed out and discussed. Synergistic effects of VitC and chosen polyphenols on amyloid fibrilllation of human stB have been explored and are reported here for the first time.

scholarly journals Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro

2021 ◽  
Vol 22 (21) ◽  
pp. 11484
Author(s):  
Masatoshi Inden ◽  
Ayaka Takagi ◽  
Hazuki Kitai ◽  
Taisei Ito ◽  
Hisaka Kurita ◽  
...  
Keyword(s):  
Amyloid Fibril ◽  
Therapeutic Potential ◽  
Neuroprotective Effect ◽  
Neuronal Cell Death ◽  
Lewy Bodies ◽  
Neuronal Cell ◽  
Therapeutic Agents ◽  
Amyloid Fibril Formation ◽  
Transcription Factor Eb

Aggregation of α-synuclein (α-Syn) is implicated in the pathogenesis of Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Therefore, the removal of α-Syn aggregation could lead to the development of many new therapeutic agents for neurodegenerative diseases. In the present study, we succeeded in generating a new α-Syn stably expressing cell line using a piggyBac transposon system to investigate the neuroprotective effect of the flavonoid kaempferol on α-Syn toxicity. We found that kaempferol provided significant protection against α-Syn-related neurotoxicity. Furthermore, kaempferol induced autophagy through an increase in the biogenesis of lysosomes by inducing the expression of transcription factor EB and reducing the accumulation of α-Syn; thus, kaempferol prevented neuronal cell death. Moreover, kaempferol directly blocked the amyloid fibril formation of α-Syn. These results support the therapeutic potential of kaempferol in diseases such as synucleinopathies that are characterized by α-Syn aggregates.

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