Understanding Amyloid Structures and Disease: A Continuing Challenge in Health Research

Chiellini, Grazia

doi:10.3390/ijms22126620

Cited by 4 publications

(8 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As mentioned in the introduction, the nature of neurodegenerative diseases, including Alzheimer’s disease, is largely related to amyloid Aβ42 [ 1 , 2 , 3 , 4 ]. At the same time, research of this amyloid is carried out in several directions, on the one hand, the toxicity of oligomers of this amyloid relative to brain cells is studied [ 5 , 6 , 7 , 8 , 9 , 10 , 11 ], and on the other hand, its structure is explored [ 3 , 4 , 9 ]. One of the main questions: how does the structure of this peptide change when of L-amino acids are replaced by D-analog?…”

Section: Chiral Inversion (Ci) In Model Systems and The Possible CI R...mentioning

confidence: 99%

“…Another important question concerns the mechanism of such a replacement—spontaneous chiral inversion occurring in proteins and peptides of elderly patients with neurodegenerative diseases [ 2 , 4 ]. The works carried out in this direction have not yet led to the establishment of the CI molecular mechanisms, but have already demonstrated the significance of this process for the amyloids toxicity [ 22 , 23 , 24 , 25 ].…”

Section: Chiral Inversion (Ci) In Model Systems and The Possible CI R...mentioning

confidence: 99%

“…The choice of NSAIDs is not accidental, since the derivatives of these drugs are now being tested as inhibitor of γ-secretase-a complex of enzymes involved in the synthesis of Aβ42 from precursor of amyloid protein (APP) [18,19]. The mechanisms of the Aβ42 monomer action and its aggregated forms have been studied in cell models, while the primary cause of the formation of aggregates and their relationship with the inclusion of D-amino acids in biomolecules remains to be studied [3,4,[9][10][11]. This review describes first results on the influence of D-amino acids on the structure and properties, obtained in the study of model systems (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…The source of this interest is associated with the fact that one of the main causes of neurodegenerative diseases (Alzheimer’s, Parkinson’s, and some others) is due to the replacement in certain proteins and peptides of L-amino acids to D-analogs, which occurs during aging [ 1 , 2 ]. It is these proteins and peptides are believed to undergo disruptions in folding processes, such as aggregation resulted in the formation of large oligomers and fibrils that are highly toxic, especially, for the brain cells [ 3 , 4 ]. So, β-amyloid (Aβ42), a 39–42 amino acid polypeptide found in the brain, being present in a high concentration in the central nervous system, penetrates the membranes of astrocytes, forming special channels through which it affects the level of extracellular calcium [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…The mechanisms of the Aβ42 monomer action and its aggregated forms have been studied in cell models, while the primary cause of the formation of aggregates and their relationship with the inclusion of D-amino acids in biomolecules remains to be studied [ 3 , 4 , 9 , 10 , 11 ]. This review describes first results on the influence of D-amino acids on the structure and properties, obtained in the study of model systems ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Chiral Linked Systems as a Model for Understanding D-Amino Acids Influence on the Structure and Properties of Amyloid Peptides

Ageeva

Doktorov

Polyakov

et al. 2022

IJMS

View full text Add to dashboard Cite

In this review, we provide an illustration of the idea discussed in the literature of using model compounds to study the effect of substitution of L- for D-amino acid residues in amyloid peptides. The need for modeling is due to the inability to study highly disordered peptides by traditional methods (high-field NMR, X-ray). At the same time, the appearance of such peptides, where L-amino acids are partially replaced by D-analogs is one of the main causes of Alzheimer’s disease. The review presents examples of the use diastereomers with L-/D-tryptophan in model process—photoinduced electron transfer (ET) for studying differences in reactivity and structure of systems with L- and D-optical isomers. The combined application of spin effects, including those calculated using the original theory, fluorescence techniques and molecular modeling has demonstrated a real difference in the structure and efficiency of ET in diastereomers with L-/D-tryptophan residues. In addition, the review compared the factors governing chiral inversion in model metallopeptides and Aβ42 amyloid.

show abstract

Section: Chiral Inversion (Ci) In Model Systems and The Possible CI R...mentioning

confidence: 99%

Section: Chiral Inversion (Ci) In Model Systems and The Possible CI R...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Chiral Linked Systems as a Model for Understanding D-Amino Acids Influence on the Structure and Properties of Amyloid Peptides

Ageeva

Doktorov

Polyakov

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

Amyloid, a Jekyll and Hyde Molecule Inducing Neuronal Decline and Cognitive Dysfunction is Also a Unique Molecular Template used in Nano-electronics, Light Capture Photovoltaics, and Biosensors in Neuromorphic Computing.

Melrose,

Smith

2024

Preprint

View full text Add to dashboard Cite

Amyloid self-assembled from amyloid peptides βΑ40 or βΑ42 is notorious for its neurotoxic effects in plaque and neurofibrillary tangle formations leading to neuron dysfunction and diseases of cognitive decline (e.g. Alzheimer’s, Parkinson’s and Huntington's disease). This contrasts with so-called functional amyloids which are non-toxic ordered template structures amenable to applications in tissue engineering. Amyloid fibrils of variable morphology including long and hollow fibres and flattened tube and spiral ribbon-like structures have been used in engineering applications in nano-biology. Protein assemblies based on amyloid core structures display diverse biological functionalities could be applied in futuristic self-assembling biomaterials in nano-electronics. These possibilities have revolutionized the development of next generation computers and biosensors, ultracapacitors, memristors, actuators, molecular switches and could also be used to develop artificial synapses. Amyloid fibril assemblies have also been used in photoelectric and photon capture light harvesting technologies and been applied in innovative nano-photoelectronics and photovoltaics. Hybrid Aβ(16–22)-α-synuclein amyloid fibrils also exhibit light-harvesting and electron-transfer properties. Engineered amyloid assemblies are thus facilitating innovative futuristic advances in nano-technology. Furthermore, with a better understanding of amyloid fibril assembly processes it may be possible to develop therapeutic methods that prevent the toxic build up of this polymer in brain tissues that leads to diseases of cognitive decline. With the ever-expanding prevalence of these diseases in the ageing general global population, there certainly is a clear and present need to find a remedy for these debilitating conditions.

show abstract

Photoinduced Processes in Lysine-Tryptophan-Lysine Tripeptide with L and D Tryptophan

Ageeva

Lukyanov

Martyanova

et al. 2023

IJMS

View full text Add to dashboard Cite

Optical isomers of short peptide Lysine-Tryptophan-Lysine (Lys-{L/D-Trp}-Lys) and Lys-Trp-Lys with an acetate counter-ion were used to study photoinduced intramolecular and intermolecular processes of interest in photobiology. A comparison of L- and D-amino acid reactivity is also the focus of scientists’ attention in various specialties because today, the presence of amyloid proteins with D-amino acids in the human brain is considered one of the leading causes of Alzheimer’s disease. Since aggregated amyloids, mainly Aβ42, are highly disordered peptides that cannot be studied with traditional NMR and X-ray techniques, it is trending to explore the reasons for differences between L- and D-amino acids using short peptides, as in our article. Using NMR, chemically induced dynamic nuclear polarization (CIDNP) and fluorescence techniques allowed us to detect the influence of tryptophan (Trp) optical configuration on the peptides fluorescence quantum yields, bimolecular quenching rates of Trp excited state, and the photocleavage products formation. Thus, compared with the D-analog, the L-isomer shows a greater Trp excited state quenching efficiency with the electron transfer (ET) mechanism. There are experimental confirmations of the hypothesis about photoinduced ET between Trp and the CONH peptide bond, as well as between Trp and another amide group.

show abstract

Understanding Amyloid Structures and Disease: A Continuing Challenge in Health Research

Abstract: Neurodegenerative disorders (NDDs), including Alzheimer’s, Parkinson’s, and Huntington’s diseases, are a highly prevalent class of disorders that share the presence of aberrant aggregates called amyloids in the nervous system [...]

Cited by 4 publications

References 28 publications

Chiral Linked Systems as a Model for Understanding D-Amino Acids Influence on the Structure and Properties of Amyloid Peptides

Chiral Linked Systems as a Model for Understanding D-Amino Acids Influence on the Structure and Properties of Amyloid Peptides

Amyloid, a Jekyll and Hyde Molecule Inducing Neuronal Decline and Cognitive Dysfunction is Also a Unique Molecular Template used in Nano-electronics, Light Capture Photovoltaics, and Biosensors in Neuromorphic Computing.

Photoinduced Processes in Lysine-Tryptophan-Lysine Tripeptide with L and D Tryptophan

Contact Info

Product

Resources

About