Inhibition and Degradation of Amyloid Beta (Aβ40) Fibrillation by Designed Small Peptide: A Combined Spectroscopy, Microscopy, and Cell Toxicity Study

Ghosh, Anirban; Pradhan, Nibedita; Bera, Swapna; Datta, Aritreyee; Krishnamoorthy, Janarthanan; Jana, Nikhil R.; Bhunia, Anirban

doi:10.1021/acschemneuro.6b00349

Cited by 46 publications

(29 citation statements)

References 29 publications

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“…To this aim, several natural antioxidants as silymarin, bacoside-A, and resveratrol have evidenced antioxidant effects and are currently under clinical investigation [24,25,26,27]. Among natural antioxidants, Panax ginseng C.A.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells

Liu

Bai

et al. 2019

Molecules

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Accumulation of amyloid-β (Aβ), which results in the formation of senile plaques that cause oxidative damage and neuronal cell death, has been accepted as the major pathological mechanism of Alzheimer’s disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis represents the effective strategies in combating AD. Ginsenoside Re (Re) has pharmacological effects against Aβ-induced neurotoxicity. However, its molecular mechanism remains elusive. The present study evaluated the effect of Re against Aβ-induced cytotoxicity and apoptosis in SH-SY5Y cells, and investigated the underlying mechanism. We demonstrate that Re inhibits the Aβ-triggered mitochondrial apoptotic pathway, as indicated by maintenance of mitochondrial functional, elevated Bcl-2/Bax ratio, reduced cytochrome c release, and inactivation of caspase-3/9. Re attenuated Aβ-evoked reactive oxygen species (ROS) production, apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, and JNK activation. ROS-scavenging abrogated the ability of Re to alter ASK-1 activation. Simultaneously, inhibition of JNK abolished Re-induced Bax downregulation in Aβ-challenged SH-SY5Y cells. In addition, Re enhanced activation of the nuclear factor-E2-related factor 2 (Nrf2) in Aβ-induced SH-SY5Y cells. Knockdown of Nrf2 by small interfering RNA targeting Nrf2 abolished the protective effect of Re. Our findings indicate that Re could be a potential therapeutic approach for the treatment of AD.

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Section: Introductionmentioning

confidence: 99%

Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells

Liu

Bai

et al. 2019

Molecules

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“…A recent study by Ghosh et al . showed the ability of an 11-mer peptide (NF11) to interact with the N-terminus region as well as the central hydrophobic cluster of Aβ40 to stop fibrillization and diminish existing mature fibrils 25 . Clearly, there is an interest to find potent molecules with “dual functionalities” i.e.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic insights into remodeled Tau-derived PHF6 peptide fibrils by Naphthoquinone-Tryptophan hybrids

KrishnaKumar

Paul

Gazit

et al. 2018

Sci Rep

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Intra-cellular tau protein tangles and extra-cellular β-amyloid plaques are hallmarks of Alzheimer’s disease (AD), characterized by the conversion of natively unfolded monomeric protein/peptide into misfolded β-sheet rich aggregates. Therefore, inhibiting the aggregation cascade or disassembling the pre-formed aggregates becomes a pivotal event in disease treatment. In the present study, we show that Naphthoquinone-Tryptophan hybrids, i.e., NQTrp and Cl-NQTrp significantly disrupted the pre-formed fibrillar aggregates of Tau-derived PHF6 (VQIVYK) peptide and full-length tau protein in vitro, in a dose-dependent manner as evident from ThS assay, CD spectroscopy, and TEM. Molecular dynamics simulation of PHF6 oligomers and fibrils with the Naphthoquinone-Tryptophan hybrids provides a possible structure-function based mechanism-of-action, highlighting the role of hydrophobic interaction and hydrogen bond formation during fibril disassembly. These findings signify the effectiveness of NQTrp and Cl-NQTrp in disassembling fibrillar aggregates and may help in designing novel hybrid molecules for AD treatment.

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“…59 Similarly, prostatespecific antigen and matriptase, which are proteases in seminal plasma degraded SEVI amyloid fibrils. 60 A recent study showed disaggregation of Ab(1-40) amyloid fibrils by nonhemolytic 11-residue peptide (NAVRWSLMRPF), 61 which suggested the possible application of this short peptide for eliminating SEVI amyloid fibrils and peptidomimetic therapeutic agents against amyloid disease.…”

Section: Reverse and Dissociate Sevi Amyloid Fibrils (Methods 3)mentioning

confidence: 99%

“…78 In addition, nonhemolytic 11-residue peptides inhibited the formation of Ab(1-40) amyloid fibrils by interacting with the N-terminal part and the central hydrophobic cluster of Ab . 61…”

Section: Stabilization Of Sevi Precursors (Methods 7)mentioning

confidence: 99%

“…A recent study demonstrated that brazilin, a natural compound that is isolated from Caesalpinia sappan , bound to SEVI precursors and inhibited amyloid formation at lower concentrations than EGCG . In addition, nonhemolytic 11‐residue peptides inhibited the formation of Aβ(1–40) amyloid fibrils by interacting with the N‐terminal part and the central hydrophobic cluster of Aβ(1–40) …”

Section: Inhibition Of Sevi‐enhanced Hiv Viral Infectionmentioning

confidence: 99%

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Semen‐derived amyloidogenic peptides—Key players of HIV infection

Lee

Ramamoorthy

2018

Protein Science

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Misfolding and amyloid aggregation of intrinsically disordered proteins (IDPs) are implicated in a variety of diseases. Studies have shown that membrane plays important roles on the formation of intermediate structures of IDPs that can initiate (and/or speed-up) amyloid aggregation to form fibers. The process of amyloid aggregation also disrupts membrane to cause cell death in amyloid diseases like Alzheimer's disease and type-2 diabetes. On the other hand, recent studies reported the membrane fusion properties of amyloid fibers. Remarkably, amyloid-fibril formation by short peptide fragments of highly abundant prostatic acidic-phosphatase (PAP) in human semen and are capable of boosting the rate of HIV infection up to 400,000-fold during sexual contact. Unlike the least toxic fully matured fibers of most amyloid proteins, the semen-derived enhancer of virus infection (SEVI) amyloid-fibrils of PAP peptide fragments are highly potent in rendering the maximum rate of HIV infection. This unusual property of amyloid fibers has witnessed increasing number of studies on the biophysical aspects of fiber formation and fiber-membrane interactions. NMR studies have reported a highly disordered partial helical structure in a membrane environment for the intrinsically disordered PAP peptide that promotes the fusion of the viral membrane with that of host cells. The purpose of this review article is to unify and integrate biophysical and immunological research reported in the previous studies on SEVI. Specifically, amyloid aggregation, dramatic HIV infection enhancing properties, membrane fusion properties, high resolution NMR structure, and approaches to eliminate the enhancement of HIV infection of SEVI peptides are discussed.

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Inhibition and Degradation of Amyloid Beta (Aβ40) Fibrillation by Designed Small Peptide: A Combined Spectroscopy, Microscopy, and Cell Toxicity Study

Cited by 46 publications

References 29 publications

Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells

Ginsenoside Re Inhibits ROS/ASK-1 Dependent Mitochondrial Apoptosis Pathway and Activation of Nrf2-Antioxidant Response in Beta-Amyloid-Challenged SH-SY5Y Cells

Mechanistic insights into remodeled Tau-derived PHF6 peptide fibrils by Naphthoquinone-Tryptophan hybrids

Semen‐derived amyloidogenic peptides—Key players of HIV infection

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