Amyloids and Protein Aggregation—Analytical Methods

Li, Huiyuan; Rahimi, Farid; Sinha, Sharmistha; Maiti, Panchanan; Bitan, Gal; Murakami, Kazuma

doi:10.1002/9780470027318.a9038

Cited by 38 publications

(95 citation statements)

References 229 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Amyloid aggregation is accompanied by conformational change in the aggregating protein to β-sheet-rich structure57. To analyze secondary structure, far-UV (190–260 nm) CD spectra were recorded using Jasco 1500 spectropolarimeter and 1 mm path length quartz cuvette.…”

Section: Methodsmentioning

confidence: 99%

An acridine derivative, [4,5-bis{(N-carboxy methyl imidazolium)methyl}acridine] dibromide, shows anti-TDP-43 aggregation effect in ALS disease models

Prasad

Raju

Sivalingam

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with aggregation of TAR DNA-binding protein-43 (TDP-43) in neuronal cells and manifests as motor neuron dysfunction & muscle atrophy. The carboxyl-terminal prion-like domain of TDP-43 can aggregate in vitro into toxic β-sheet rich amyloid-like structures. So far, treatment options for ALS are very limited and Riluzole, which targets glutamate receptors, is the only but highly ineffective drug. Therefore, great interest exists in developing molecules for ALS treatment. Here, we have examined certain derivatives of acridine containing same side chains at position 4 & 5, for inhibitory potential against TDP-43 aggregation. Among several acridine derivatives examined, AIM4, which contains polar carboxyl groups in the side arms, significantly reduces TDP-43-YFP aggregation in the powerful yeast model cell and also abolishes in vitro amyloid-like aggregation of carboxyl terminal domain of TDP-43, as observed by AFM imaging. Thus, AIM4 can be a lead molecule potentiating further therapeutic research for ALS.

show abstract

Section: Methodsmentioning

confidence: 99%

An acridine derivative, [4,5-bis{(N-carboxy methyl imidazolium)methyl}acridine] dibromide, shows anti-TDP-43 aggregation effect in ALS disease models

Prasad

Raju

Sivalingam

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In a recent contribution, Walter et al blended the pinching capacity of a nanomechanical DNA origami forceps [158] with the biosensing capacity of split aptamer systems [159]. Indeed, the constituting sequences of the ATP-specific split aptamer were equipped with green-and red-emitting photostable cyanine dyes that act as energy donor and acceptor, respectively [160] and were subsequently appended on one arm of the DNA origami forceps.…”

Section: Aptamers As Key Components In the Fabrication Of Smart Dna Omentioning

confidence: 99%

“…Congo Red is used to stain and detect amyloid depositions in tissues. Upon binding to amyloid structures, Congo Red yields a unique blue-green birefringence under a cross-polarized light microscope [159].) Farrar et al [127] concluded that β55 may have bound smaller aggregates, including oligomers, of Aβ peripheral to the dense plaques based on their observation that β55 apparently bound low-molecular-weight oligomers of Aβ40 and Aβ42 on SDS-PAGE gels, and similar observation reported by Koffie et al [163], showing a "halo of oligomers" surrounding the plaques detected by a so-called "conformation-specific" NAB61 antibody [164].…”

Section: Aptamers and Aβmentioning

confidence: 99%

“…The shortcomings of SDS-PAGE have been highlighted in many studies of Aβ [21,60,157,159,179,181,183] and α-synuclein [173] and is gradually being appreciated in the AD field. Meanwhile, interpretations of findings about elusive Aβ oligomers has come under scrutiny and disputed to such an extent that the foundations of the oligomer cascade hypothesis have been shaken.…”

Section: Sds-page Aptamers Antibodies and "Halos Of Oligomers"mentioning

confidence: 99%

See 1 more Smart Citation

Aptamers

2018

View full text Add to dashboard Cite

“…Xray studies could provide a high-resolution structure, but for protein aggregates it is typically difficult to obtain a crystal with high diffraction quality needed for X-ray studies [129].…”

Section: Introductionmentioning

confidence: 99%

Parkinson's disease in the spotlight : unraveling nanoscale alpha-synuclein oligomers using ultrasensitive single-molecule spectroscopy

Zijlstra¹

View full text Add to dashboard Cite

Niels ZijlstraParkinson's disease in the spotlight Protein folding is an extraordinarily complex process of which the details are still unclear, but is thought to be governed by the energy landscape of the protein and involves a stochastic sampling of many different folds, or conformations, until the protein reaches its thermodynamically most favorable fold [7]. This fold is usually called the native structure of the protein and is mainly determined by the amino acid sequence of the protein [8,9], although the complex environment found in a cell is thought to influence the folding as well [10].The folding of a protein is in some cases co-translational, that is, the folding takes place during synthesis [7,11,12]. In other cases, however, the protein folds in the cytoplasm after a complete synthesis, or is first transported to specific parts of the cell, such as mitochondria or the endoplasmic reticulum, before it folds, see figure 1.1 [7,12].Given the complexity of protein folding and the enormous number of folding events in a cell, it is not surprising that sometimes a protein does not fold correctly or that a protein does not stay folded correctly [1,13]. The protein can get trapped in a local energy minimum resulting in the protein to misfold making the protein toxic [1,14].The more complex the protein folding pathway is, the more likely it is that the folding goes wrong. Normally, a cell can minimize the amount of misfolded proteins by using specialized molecular chaperones or folding catalysts to assist in the folding [4,13]. If the folding still goes wrong, the cell can get rid of the misfolded proteins by degrading them via the ubiquitin-proteasome system, see figure 1.1 [15]. Unfortunately, this defense mechanism does not always work properly. 6 1 1.2. Amyloid diseases and the oligomeric species Amyloid diseases and the oligomeric speciesProtein misfolding and the subsequent aggregation is considered to play an important role in many human neurodegenerative diseases, such as Parkinson's, Alzheimer's, and Huntington's disease, type II diabetes, and in the prion diseases [16]. These diseases are associated with the formation of inter-and intracellular inclusions that mainly contain insoluble amyloid fibrillar aggregates. Amyloid refers to the aggregates having a characteristic cross-β sheet secondary structure. These fibrils are ∼10 nm 7 1 1.2. Amyloid diseases and the oligomeric species in diameter, and can be several microns in length, and thus are composed of many thousands of the constituent monomeric proteins [17]. A commonly used method to detect the formation of amyloid aggregates uses the fluorescent dye Thioflavin T (ThioT). When ThioT binds to β-sheet-rich domains, the dye displays enhanced fluorescence intensity and a characteristic red shift of its emission spectrum. ThioT fluorescence is often used to monitor the kinetics of amyloid formation, which, in general, follows a sigmoidal growth curve that is characterized by an initial lag phase, followed by an exponential growth until it reaches a ...

show abstract

Amyloids and Protein Aggregation—Analytical Methods

Cited by 38 publications

References 229 publications

An acridine derivative, [4,5-bis{(N-carboxy methyl imidazolium)methyl}acridine] dibromide, shows anti-TDP-43 aggregation effect in ALS disease models

An acridine derivative, [4,5-bis{(N-carboxy methyl imidazolium)methyl}acridine] dibromide, shows anti-TDP-43 aggregation effect in ALS disease models

Aptamers

Parkinson's disease in the spotlight : unraveling nanoscale alpha-synuclein oligomers using ultrasensitive single-molecule spectroscopy

Contact Info

Product

Resources

About