Conversion of non-fibrillar β-sheet oligomers into amyloid fibrils in Alzheimer’s disease amyloid peptide aggregation

2007 ◽  
Vol 361 (4) ◽  
pp. 916-921 ◽  
Author(s):  
Núria Benseny-Cases ◽  
Mercedes Cócera ◽  
Josep Cladera
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Fibrils ◽  
Amyloid Peptide ◽  
Peptide Aggregation ◽  
Β Sheet

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.

β-Amyloid Peptide and Amyloid Precursor Proteins in Olfactory Mucosa of Patients with Alzheimer's Disease, Parkinson's Disease, and down Syndrome

1995 ◽  
Vol 104 (8) ◽  
pp. 655-661 ◽  
Author(s):  
Peter B. Crino ◽  
Barry Greenberg ◽  
John A. Martin ◽  
Virginia M.-Y. Lee ◽  
William D. Hill ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Down Syndrome ◽  
Amyloid Fibrils ◽  
Olfactory Mucosa ◽  
Amyloid Peptide ◽  
Β Amyloid

Dystrophic neurites are present in olfactory epithelium (OE) of patients with Alzheimer's disease (AD), Parkinson's disease (PD), and Down syndrome (DS) and occasionally in normal individuals. Cultured olfactory neuroblasts from AD patients generate carboxy terminal amyloid precursor protein (APP) fragments that contain β-amyloid (Aβ), but it is not known if deposits of Aβ and/or APP fragments occur in the OE of individuals with or without AD, PD, or DS. To determine if Aβ accumulates in the OE in situ, we probed postmortem samples of olfactory mucosa from patients with AD, PD and AD (PD/AD), and DS and AD (DS/AD), as well as from controls, using polyclonal and monoclonal antibodies to Aβ and flanking sequences in APPs. Samples of OE also were examined by thioflavin-S and electron microscopy. Labeling of Aβ was observed in 10 of 12 AD cases, 2 of 3 PD/AD cases, 3 of 4 DS/AD cases, 3 of 10 adult controls, and 4 of 6 fetal cases. The Aβ staining was seen in the basal third of the OE, in axons projecting through the lamina propria, and in metaplastic respiratory epithelium within the OE. Antibodies to other APP domains stained the OE of patients and controls. Thioflavin-S staining was present in the basal third of the OE of 8 of 9 AD patients and several PD/AD and DS/AD patients, but only in rare cells of 3 controls. Electron microscopy did not reveal amyloid fibrils in the OE. These data suggest that deposition of Aβ occurs in a variety of circumstances and is not restricted to patients with AD, PD, or DS.

Photodegradation of β-sheet amyloid fibrils associated with Alzheimer's disease by using polyoxometalates as photocatalysts

2013 ◽  
Vol 49 (97) ◽  
pp. 11394 ◽  
Author(s):  
Meng Li ◽  
Can Xu ◽  
Jinsong Ren ◽  
Enbo Wang ◽  
Xiaogang Qu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Fibrils ◽  
Β Sheet

scholarly journals Assembling amyloid fibrils from designed structures containing a significant amyloid β-peptide fragment

2002 ◽  
Vol 366 (1) ◽  
pp. 343-351 ◽  
Author(s):  
Lars O. TJERNBERG ◽  
Agneta TJERNBERG ◽  
Niklas BARK ◽  
Yuan SHI ◽  
Bela P. RUZSICSKA ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Fibrils ◽  
Amyloid Β ◽  
Structural Features ◽  
Fibril Formation ◽  
Amyloid Β Peptide ◽  
Detailed Model ◽  
Aβ Fibrils ◽  
Β Sheet

The amyloid plaque, consisting of amyloid β-peptide (Aβ) fibrils surrounded by dystrophic neurites, is an invariable feature of Alzheimer's disease. The determination of the molecular structure of Aβ fibrils is a significant goal that may lead to the structure-based design of effective therapeutics for Alzheimer's disease. Technical challenges have thus far rendered this goal impossible. In the present study, we develop an alternative methodology. Rather than determining the structure directly, we design conformationally constrained peptides and demonstrate that only certain ‘bricks’ can aggregate into fibrils morphologically identical to Aβ fibrils. The designed peptides include variants of a decapeptide fragment of Aβ, previously shown to be one of the smallest peptides that (1) includes a pentapeptide sequence necessary for Aβ—Aβ binding and aggregation and (2) can form fibrils indistinguishable from those formed by full-length Aβ. The secondary structure of these bricks is monitored by CD spectroscopy, and electron microscopy is used to study the morphology of the aggregates formed. We then made various residue deletions and substitutions to determine which structural features are essential for fibril formation. From the constraints, statistical analysis of side-chain pair correlations in β-sheets and experimental data, we deduce a detailed model of the peptide strand alignment in fibrils formed by these bricks. Our results show that the constrained decapeptide dimers rapidly form an intramolecular, antiparallel β-sheet and polymerize into amyloid fibrils at low concentrations. We suggest that the formation of an exposed β-sheet (e.g. an Aβ dimer formed by interaction in the decapeptide region) could be a rate-limiting step in fibril formation. A theoretical framework that explains the results is presented in parallel with the data.

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.

Liquid crystalline ordering of paired helical filaments in neurofibrillary tangles of Alzheimer's disease

1986 ◽  
Vol 44 ◽  
pp. 348-349
Author(s):  
D.F. Clapin ◽  
V.J.A. Montpetit
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurofibrillary Tangles ◽  
Liquid Crystalline ◽  
Amyloid Fibrils ◽  
Geometric Analysis ◽  
Paired Helical Filaments ◽  
Microscopic Level ◽  
Light Microscopic Level ◽  
Regular Spacing

Alzheimer's disease is characterized by the accumulation of abnormal filamentous proteins. The most important of these are amyloid fibrils and paired helical filaments (PHF). PHF are located intraneuronally forming bundles called neurofibrillary tangles. The designation of these structures as "tangles" is appropriate at the light microscopic level. However, localized domains within individual tangles appear to demonstrate a regular spacing which may indicate a liquid crystalline phase. The purpose of this paper is to present a statistical geometric analysis of PHF packing.

scholarly journals Prevention of Alzheimer's Disease-associated Aβ Aggregation by Rationally Designed Nonpeptidic β-Sheet Ligands

2004 ◽  
Vol 279 (46) ◽  
pp. 47497-47505 ◽  
Author(s):  
Petra Rzepecki ◽  
Luitgard Nagel-Steger ◽  
Sophie Feuerstein ◽  
Uwe Linne ◽  
Oliver Molt ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Aβ Aggregation ◽  
Β Sheet
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