scholarly journals Anti-Aggregation Property of Allicin by In Vitro and Molecular Docking Studies

2019 ◽  
Vol 13 ◽  
pp. 117906951986618 ◽  
Author(s):  
Suresh Kumar ◽  
Shivani Kumar ◽  
Heera Ram
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
Molecular Interaction ◽  
Fibril Formation ◽  
Amyloid Peptide ◽  
Peptide Aggregation ◽  
Aβ Peptide ◽  
In Silico Studies

Amyloidogenesis is the process in which amyloid beta (Aβ) peptide aggregation results in plaque formation in central nervous system (CNS) are associated with many neurological diseases such as Alzheimer’s disease. The peptide aggregation initiated from peptide monomers results in formation of dimers, tetramers, fibrils, and protofibrils. The ability of allicin, a lipid-soluble volatile organosulfur biological compound, present in freshly crushed garlic ( Allium sativum L.) to inhibit fibril formation by the Aβ peptide in vitro was investigated in the present study. Inhibition of fibrillogenesis was measured by a Thioflavin T (ThT) fluorescence assay and visualized by transmission electron microscopy (TEM). The molecular interaction between allicin and Aβ peptide was also demonstrated by in silico studies. The results show that allicin strongly inhibited Aβ fibrils by 97% at 300 µM, compared with control (Aβ only) ( P < .001). These results were further validated by visual of fibril formation by transmission microscopy and molecular interaction of amyloid peptide with allicin by molecular docking. Aβ forms favourable hydrophobic interaction with Ile32, Met35, Val36, and Val39, and oxygen of allicin forms hydrogen bond with the amino acid residue Lys28. Allicin anti-amyloidogenic property suggests that this naturally occurring compound may have potential to ameliorate and prevent Alzheimer’s disease.

Recent Progress on the Drug Development for the Treatment of Alzheimer’s Disease Especially on Inhibition of Amyloid-Peptide Aggregation

2020 ◽  
Vol 20 ◽  
Author(s):  
Yuanyuan Liu ◽  
Lin Cong ◽  
Chu Han ◽  
Bo Li ◽  
Rongji Dai
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Development ◽  
Amyloid Peptide ◽  
Research Progress ◽  
Peptide Aggregation ◽  
Aβ Peptide ◽  
Design And Synthesis ◽  
Aggregation Inhibitors ◽  
The Brain

: As the world's population is ageing, Alzheimer’s disease (AD) has become a big concern since patients suffering from AD have become younger and the population of AD patients is increasing worldwide. It has been revealed that the neuropathological hallmarks of AD are typically characterized by the presence of neurotoxic extracellular amyloid plaques in the brain, which are surrounded by tangles of neuronal neuronal fibers. However, the causes of AD have not been completely understood yet. Currently, there is no drug to effectively prevent AD or to completely reserve the symptoms in the patients. This article reviews the pathological features associated with AD, the recent research progress on the drug development to treat AD especially on discovery of natural product derivatives to inhibit Aβ peptide aggregation as well as design and synthesis of Aβ peptide aggregation inhibitors to treat AD.

Neuroprotective effects of bergenin in Alzheimer’s disease: Investigation through molecular docking, in vitro and in vivo studies

2019 ◽  
Vol 356 ◽  
pp. 18-40 ◽  
Author(s):  
Priyal Barai ◽  
Nisith Raval ◽  
Sanjeev Acharya ◽  
Ankit Borisa ◽  
Hardik Bhatt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
In Vivo Studies ◽  
Neuroprotective Effects

scholarly journals Multi-target-directed phenol–triazole ligands as therapeutic agents for Alzheimer's disease

2017 ◽  
Vol 8 (8) ◽  
pp. 5636-5643 ◽  
Author(s):  
Michael R. Jones ◽  
Emilie Mathieu ◽  
Christine Dyrager ◽  
Simon Faissner ◽  
Zavier Vaillancourt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Agents ◽  
Peptide Aggregation ◽  
Primary Neurons ◽  
Aβ Peptide

A series of multi-target-directed ligands are described that bind Cu, act as antioxidants, modulate Aβ peptide aggregation, and abolish Aβ toxicity in primary neurons.

Cerebrospinal fluid of Alzheimer's disease and dementia with Lewy bodies patients enhances α-synuclein fibril formation in vitro

2007 ◽  
Vol 203 (2) ◽  
pp. 579-583 ◽  
Author(s):  
Kenjiro Ono ◽  
Moeko Noguchi-Shinohara ◽  
Mitsuhiro Yoshita ◽  
Hironobu Naiki ◽  
Masahito Yamada
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Fibril Formation

scholarly journals Activation of the factor XII-driven contact system in Alzheimer’s disease patient and mouse model plasma

2015 ◽  
Vol 112 (13) ◽  
pp. 4068-4073 ◽  
Author(s):  
Daria Zamolodchikov ◽  
Zu-Lin Chen ◽  
Brooke A. Conti ◽  
Thomas Renné ◽  
Sidney Strickland
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Disease Patient ◽  
Contact System ◽  
Amyloid Peptide ◽  
Factor Xii ◽  
Contact Activation ◽  
System Activation

Alzheimer’s disease (AD) is characterized by accumulation of the β-amyloid peptide (Aβ), which likely contributes to disease via multiple mechanisms. Increasing evidence implicates inflammation in AD, the origins of which are not completely understood. We investigated whether circulating Aβ could initiate inflammation in AD via the plasma contact activation system. This proteolytic cascade is triggered by the activation of the plasma protein factor XII (FXII) and leads to kallikrein-mediated cleavage of high molecular-weight kininogen (HK) and release of proinflammatory bradykinin. Aβ has been shown to promote FXII-dependent cleavage of HK in vitro. In addition, increased cleavage of HK has been found in the cerebrospinal fluid of patients with AD. Here, we show increased activation of FXII, kallikrein activity, and HK cleavage in AD patient plasma. Increased contact system activation is also observed in AD mouse model plasma and in plasma from wild-type mice i.v. injected with Aβ42. Our results demonstrate that Aβ42-mediated contact system activation can occur in the AD circulation and suggest new pathogenic mechanisms, diagnostic tests, and therapies for AD.

scholarly journals Fibrillogenesis in Alzheimer's disease of amyloid β peptides and apolipoprotein E

1995 ◽  
Vol 306 (2) ◽  
pp. 599-604 ◽  
Author(s):  
E M Castano ◽  
F Prelli ◽  
T Wisniewski ◽  
A Golabek ◽  
R A Kumar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Late Onset ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Fibril Formation ◽  
Tau Proteins ◽  
Amyloid Formation

A central event in Alzheimer's disease is the conformational change from normally circulating soluble amyloid beta peptides (A beta) and tau proteins into amyloid fibrils, in the form of senile plaques and neurofibrillary tangles respectively. The apolipoprotein E (apoE) gene locus has recently been associated with late-onset Alzheimer's disease. It is not know whether apoE plays a direct role in the pathogenesis of the disease. In the present work we have investigated whether apoE can affect the known spontaneous in vitro formation of amyloid-like fibrils by synthetic A beta analogues using a thioflavine-T assay for fibril formation, electron microscopy and Congo Red staining. Our results show that, under the conditions used, apoE directly promotes amyloid fibril formation, increasing both the rate of fibrillogenesis and the total amount of amyloid formed. ApoE accelerated fibril formation of both wild-type A beta-(1-40) and A beta-(1-40A), an analogue created by the replacement of valine with alanine at residue 18, which alone produces few amyloid-like fibrils. However, apoE produced only a minimal effect on A beta-(1-40Q), found in the Dutch variant of Alzheimer's disease. When recombinant apoE isoforms were used, apoE4 was more efficient than apoE3 at enhancing amyloid formation. These in vitro observations support the hypothesis that apoE acts as a pathological chaperone, promoting the beta-pleated-sheet conformation of soluble A beta into amyloid fibres, and provide a possible explanation for the association of the apoE4 genetic isoform with Alzheimer's disease.

scholarly journals Bidirectional regulation of Aβ levels by Presenilin 1

2017 ◽  
Vol 114 (27) ◽  
pp. 7142-7147 ◽  
Author(s):  
Victor Bustos ◽  
Maria V. Pulina ◽  
Yildiz Kelahmetoglu ◽  
Subhash C. Sinha ◽  
Fred S. Gorelick ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cultured Cells ◽  
Amyloid Peptide ◽  
Presenilin 1 ◽  
Aβ Peptide ◽  
Bifunctional Mechanism ◽  
Bidirectional Regulation ◽  
Plaque Load

Alzheimer’s disease (AD) is characterized by accumulation of the β-amyloid peptide (Aβ), which is generated through sequential proteolysis of the amyloid precursor protein (APP), first by the action of β-secretase, generating the β-C-terminal fragment (βCTF), and then by the Presenilin 1 (PS1) enzyme in the γ-secretase complex, generating Aβ. γ-Secretase is an intramembranous protein complex composed of Aph1, Pen2, Nicastrin, and Presenilin 1. Although it has a central role in the pathogenesis of AD, knowledge of the mechanisms that regulate PS1 function is limited. Here, we show that phosphorylation of PS1 at Ser367 does not affect γ-secretase activity, but has a dramatic effect on Aβ levels in vivo. We identified CK1γ2 as the endogenous kinase responsible for the phosphorylation of PS1 at Ser367. Inhibition of CK1γ leads to a decrease in PS1 Ser367 phosphorylation and an increase in Aβ levels in cultured cells. Transgenic mice in which Ser367 of PS1 was mutated to Ala, show dramatic increases in Aβ peptide and in βCTF levels in vivo. Finally, we show that this mutation impairs the autophagic degradation of βCTF, resulting in its accumulation and increased levels of Aβ peptide and plaque load in the brain. Our results demonstrate that PS1 regulates Aβ levels by a unique bifunctional mechanism. In addition to its known role as the catalytic subunit of the γ-secretase complex, selective phosphorylation of PS1 on Ser367 also decreases Aβ levels by increasing βCTF degradation through autophagy. Elucidation of the mechanism by which PS1 regulates βCTF degradation may aid in the development of potential therapies for Alzheimer’s disease.

Synthesis, in vitro evaluation and molecular docking of a new class of indolylpropyl benzamidopiperazines as dual AChE and SERT ligands for Alzheimer’s disease

2020 ◽  
Vol 198 ◽  
pp. 112368 ◽  
Author(s):  
Julio Rodríguez-Lavado ◽  
Carlos Gallardo-Garrido ◽  
Michael Mallea ◽  
Victor Bustos ◽  
Rodrigo Osorio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Docking ◽  
In Vitro Evaluation ◽  
New Class

scholarly journals Oil Palm Phenolics Inhibit theIn VitroAggregation ofβ-Amyloid Peptide into Oligomeric Complexes

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Robert P. Weinberg ◽  
Vera V. Koledova ◽  
Hyeari Shin ◽  
Jennifer H. Park ◽  
Yew Ai Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Oil Palm ◽  
Elaeis Guineensis ◽  
Genetically Engineered ◽  
Amyloid Peptide ◽  
Palm Tree ◽  
Transgenic Yeast ◽  
Oil Palm Phenolics

Alzheimer’s disease is a severe neurodegenerative disease characterized by the aggregation of amyloid-βpeptide (Aβ) into toxic oligomers which activate microglia and astrocytes causing acute neuroinflammation. Multiple studies show that the soluble oligomers of Aβ42 are neurotoxic and proinflammatory, whereas the monomers and insoluble fibrils are relatively nontoxic. We show that Aβ42 aggregation is inhibitedin vitroby oil palm phenolics (OPP), an aqueous extract from the oil palm tree(Elaeis guineensis). The data shows that OPP inhibits stacking ofβ-pleated sheets, which is essential for oligomerization. We demonstrate the inhibition of Aβ42 aggregation by (1) mass spectrometry; (2) Congo Red dye binding; (3) 2D-IR spectroscopy; (4) dynamic light scattering; (5) transmission electron microscopy; and (6) transgenic yeast rescue assay. In the yeast rescue assay, OPP significantly reduces the cytotoxicity of aggregating neuropeptides in yeast genetically engineered to overexpress these peptides. The data shows that OPP inhibits (1) the aggregation of Aβinto oligomers; (2) stacking ofβ-pleated sheets; and (3) fibrillar growth and coalescence. These inhibitory effects prevent the formation of neurotoxic oligomers and hold potential as a means to reduce neuroinflammation and neuronal death and thereby may play some role in the prevention or treatment of Alzheimer’s disease.

Sign in / Sign up

Export Citation Format

Share Document