Oligomers Are Promising Targets for Drug Development in the Treatment of Proteinopathies

Galzitskaya, Oxana V.

doi:10.3389/fnmol.2019.00319

Cited by 16 publications

(29 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The full-length S1 protein has a high mobility of individual protein domains and a tendency to aggregation, which creates problems for establishing its three-dimensional structure [ 203 , 204 ]. At the same time, using computational and experimental approaches, we described specific amyloidogenic regions within the domains of the S1 protein, which can be potential sites for modulating the aggregation properties of bacterial ribosomal S1 proteins [ 9 , 205 , 206 , 207 ]. Based on the predicted amyloidogenic regions, amyloidogenic peptides were synthesized, some of which exhibited antimicrobial activity in vitro tests [ 16 ].…”

Section: Mechanisms Of Antimicrobial Action Of Peptidesmentioning

confidence: 99%

“…Of particular interest is the potential for the use of peptides, which, in addition to pronounced antimicrobial properties, also tend to self-assembly, the formation of supramolecular complexes, and amyloidogenesis [ 5 , 6 , 7 ]. Traditionally, the amyloidogenic properties of peptides are negatively regarded as contributing to the development of neurodegenerative and progressive metabolic diseases [ 8 , 9 , 10 ]. However, in recent years, more and more attention has been paid to the study of the functional role of amyloidogenic peptides in the protection of the host and the prospects for their use as antimicrobial agents [ 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antimicrobial and Amyloidogenic Activity of Peptides. Can Antimicrobial Peptides Be Used against SARS-CoV-2?

Kurpe

Grishin

Surin

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

At present, much attention is paid to the use of antimicrobial peptides (AMPs) of natural and artificial origin to combat pathogens. AMPs have several points that determine their biological activity. We analyzed the structural properties of AMPs, as well as described their mechanism of action and impact on pathogenic bacteria and viruses. Recently published data on the development of new AMP drugs based on a combination of molecular design and genetic engineering approaches are presented. In this article, we have focused on information on the amyloidogenic properties of AMP. This review examines AMP development strategies from the perspective of the current high prevalence of antibiotic-resistant bacteria, and the potential prospects and challenges of using AMPs against infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

show abstract

Section: Mechanisms Of Antimicrobial Action Of Peptidesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antimicrobial and Amyloidogenic Activity of Peptides. Can Antimicrobial Peptides Be Used against SARS-CoV-2?

Kurpe

Grishin

Surin

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this regard, the propensity of some proteins and peptides to form oligomers without fibril formation, as expected, can be used to predict their amyloidogenicity, as was suggested [ 22 ]. Previously, it was shown that the formation of oligomers is a key event that determines the pathway of fibrillation [ 23 , 44 , 45 ], as well as a polymorphism of fibrils [ 46 , 47 , 48 ].…”

Section: Discussionmentioning

confidence: 99%

Multiple Antimicrobial Effects of Hybrid Peptides Synthesized Based on the Sequence of Ribosomal S1 Protein from Staphylococcus aureus

Кравченко

Domnin

Grishin

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

The need to develop new antimicrobial peptides is due to the high resistance of pathogenic bacteria to traditional antibiotics now and in the future. The creation of synthetic peptide constructs is a common and successful approach to the development of new antimicrobial peptides. In this work, we use a simple, flexible, and scalable technique to create hybrid antimicrobial peptides containing amyloidogenic regions of the ribosomal S1 protein from Staphylococcus aureus. While the cell-penetrating peptide allows the peptide to enter the bacterial cell, the amyloidogenic site provides an antimicrobial effect by coaggregating with functional bacterial proteins. We have demonstrated the antimicrobial effects of the R23F, R23DI, and R23EI hybrid peptides against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli, and Bacillus cereus. R23F, R23DI, and R23EI can be used as antimicrobial peptides against Gram-positive and Gram-negative bacteria resistant to traditional antibiotics.

show abstract

“…The misfolding and extracellular aggregation of Aβ peptides have been recognized as the main cause of AD progression, leading to the formation of toxic Aβ oligomers and deposition of β-amyloid plaques in the brain [61]. It has been suggested that oligomeric Aβ species may represent a valid biological target [66,155,156].…”

Section: Misfolded Aβ In Admentioning

confidence: 99%

Green Tea Epigallocatechin-3-gallate (EGCG) Targeting Protein Misfolding in Drug Discovery for Neurodegenerative Diseases

2021

View full text Add to dashboard Cite

The potential to treat neurodegenerative diseases (NDs) of the major bioactive compound of green tea, epigallocatechin-3-gallate (EGCG), is well documented. Numerous findings now suggest that EGCG targets protein misfolding and aggregation, a common cause and pathological mechanism in many NDs. Several studies have shown that EGCG interacts with misfolded proteins such as amyloid beta-peptide (Aβ), linked to Alzheimer’s disease (AD), and α-synuclein, linked to Parkinson’s disease (PD). To date, NDs constitute a serious public health problem, causing a financial burden for health care systems worldwide. Although current treatments provide symptomatic relief, they do not stop or even slow the progression of these devastating disorders. Therefore, there is an urgent need to develop effective drugs for these incurable ailments. It is expected that targeting protein misfolding can serve as a therapeutic strategy for many NDs since protein misfolding is a common cause of neurodegeneration. In this context, EGCG may offer great potential opportunities in drug discovery for NDs. Therefore, this review critically discusses the role of EGCG in NDs drug discovery and provides updated information on the scientific evidence that EGCG can potentially be used to treat many of these fatal brain disorders.

show abstract

Oligomers Are Promising Targets for Drug Development in the Treatment of Proteinopathies

Cited by 16 publications

References 69 publications

Antimicrobial and Amyloidogenic Activity of Peptides. Can Antimicrobial Peptides Be Used against SARS-CoV-2?

Antimicrobial and Amyloidogenic Activity of Peptides. Can Antimicrobial Peptides Be Used against SARS-CoV-2?

Multiple Antimicrobial Effects of Hybrid Peptides Synthesized Based on the Sequence of Ribosomal S1 Protein from Staphylococcus aureus

Green Tea Epigallocatechin-3-gallate (EGCG) Targeting Protein Misfolding in Drug Discovery for Neurodegenerative Diseases

Contact Info

Product

Resources

About