Innovative IgG Biomarkers Based on Phage Display Microbial Amyloid Mimotope for State and Stage Diagnosis in Alzheimer’s Disease

Plano, Laura M. De; Carnazza, Santina; Franco, Domenico; Rizzo, Maria Giovanna; Conoci, Sabrina; Petralia, Salvatore; Zappia, Mario; Campolo, Michela; Esposito, Emanuela; Cuzzocrea, Salvatore; Guglielmino, Salvatore

doi:10.1021/acschemneuro.9b00549

Cited by 18 publications

(18 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 2020, Plano et al . performed a double binding phage display selection to identify new conformation antigens of Aβ 1-42 by alternating biopanning with AD serum and monoclonal antibody YPF19 (chosen as like Aβ-amyloid structure protein), which can be used as novel diagnostic biomarkers for the diagnosis of AD patients 111 . Compared with wild-type phage M13, the selected recombinant phage clone 12III1 showed a greater ability to prevent amyloid aggregation and promote disaggregation of preformed fibrils 112 .…”

Section: Phage Display Technology For Ad Early Diagnosismentioning

confidence: 99%

Phage display derived peptides for Alzheimer's disease therapy and diagnosis

Zhang¹,

Zhang²,

Gao³

et al. 2022

Theranostics

View full text Add to dashboard Cite

Alzheimer's disease (AD) is an incurable and fatal progressive neurodegenerative disorder associated with memory and cognition impairment. AD is one of the top medical care concerns across the world with a projected economic burden of $2 trillion by 2030. To date, however, there remains no effective disease-modifying therapy available. It is more important than ever to reveal novel therapeutic approaches. Peptide-based biotherapeutics has been a great potential strategy attributed to their distinct and superior biochemical characteristics, such as reproducible chemical synthesis and modification, rapid cell and tissue permeability, and fast blood clearance. Phage display, one of today's most powerful platforms, allows selection and identification of suitable peptide drug candidates with high affinities and specificity toward target, demonstrating the potential to overcome challenges and limitations in AD diagnosis/treatment. We aim to provide the first comprehensive review to summarize the status in this research direction. The biological overview of phage display is described, including basic biology of the phage vectors and construction principle of phage library, biopanning procedure, mirror image phage display, and various binding affinity evaluation approaches. Further, the applications of phage display in AD therapy, targeted drug delivery, and early detection are presented. Finally, we discuss the current challenges and offer a future outlook for further advancing the potential application of phage display on AD and other neurodegenerative diseases.

show abstract

Section: Phage Display Technology For Ad Early Diagnosismentioning

confidence: 99%

Phage display derived peptides for Alzheimer's disease therapy and diagnosis

Zhang¹,

Zhang²,

Gao³

et al. 2022

Theranostics

View full text Add to dashboard Cite

show abstract

“…pC89 (M13 wild-type vector without peptide insert) and two engineered phage clones with different amino acid sequences of the foreign peptide were used. Specifically, the P9b phage clone displayed the sequence QRKLAAKLT [41], while the 12III1 the sequence RWPPHFEWHFDD [42]. Propagation of pC89 and engineered phage clones was carried out in Escherichia coli TG1 bacterial host (Lac-Z deleted).…”

Section: Bacteriophagesmentioning

confidence: 99%

Role of Phage Capsid in the Resistance to UV-C Radiations

Plano

Franco

Rizzo

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

The conformational variation of the viral capsid structure plays an essential role both for the environmental resistance and acid nuclear release during cellular infection. The aim of this study was to evaluate how capsid rearrangement in engineered phages of M13 protects viral DNA and peptide bonds from damage induced by UV-C radiation. From in silico 3D modelling analysis, two M13 engineered phage clones, namely P9b and 12III1, were chosen for (i) chemical features of amino acids sequences, (ii) rearrangements in the secondary structure of their pVIII proteins and (iii) in turn the interactions involved in phage capsid. Then, their resistance to UV-C radiation and hydrogen peroxide (H2O2) was compared to M13 wild-type vector (pC89) without peptide insert. Results showed that both the phage clones acquired an advantage against direct radiation damage, due to a reorganization of interactions in the capsid for an increase of H-bond and steric interactions. However, only P9b had an increase in resistance against H2O2. These results could help to understand the molecular mechanisms involved in the stability of new virus variants, also providing quick and necessary information to develop effective protocols in the virus inactivation for human activities, such as safety foods and animal-derived materials.

show abstract

“…In addition, 12III1 phage clone was obtained by screening of 12-mer phage library against anti-Caf1 monoclonal antibody and IgGs from AD-patients, in alternate biopanning cycles, named "double binding" selection. 12III1 display the 12 amino acid sequence, RWPPHFEWHFDD, able to detect IgG levels correlated with Alzheimer disease [34]. All radiation tests were carried out using the insert-less pC89 vector as wild-type virus variant.…”

Section: Bacteriophagesmentioning

confidence: 99%

Incidence of Phage Capsid Organization on the Resistance to High Energy Proton Beams

et al. 2022

Self Cite

View full text Add to dashboard Cite

The helical geometry of virus capsid allows simple self-assembly of identical protein subunits with a low request of free energy and a similar spiral path to virus nucleic acid. Consequently, small variations in protein subunits can affect the stability of the entire phage particle. Previously, we observed that rearrangement in the capsid structure of M13 engineered phages affected the resistance to UV-C exposure, while that to H2O2 was mainly ascribable to the amino acids’ sequence of the foreign peptide. Based on these findings, in this work, the resistance to accelerated proton beam exposure (5.0 MeV energy) of the same phage clones was determined at different absorbed doses and dose rates. Then, the number of viral particles able to infect and replicate in the natural host, Escherichia coli F+, was evaluated. By comparing the results with the M13 wild-type vector (pC89), we observed that 12III1 phage clones, with the foreign peptide containing amino acids favorable to carbonylation, exhibited the highest reduction in phage titer associated with a radiation damage (RD) of 35 × 10−3/Gy at 50 dose Gy. On the other hand, P9b phage clones, containing amino acids unfavorable to carbonylation, showed the lowest reduction with an RD of 4.83 × 10−3/Gy at 500 dose Gy. These findings could improve the understanding of the molecular mechanisms underlying the radiation resistance of viruses

show abstract

Innovative IgG Biomarkers Based on Phage Display Microbial Amyloid Mimotope for State and Stage Diagnosis in Alzheimer’s Disease

Cited by 18 publications

References 74 publications

Phage display derived peptides for Alzheimer's disease therapy and diagnosis

Phage display derived peptides for Alzheimer's disease therapy and diagnosis

Role of Phage Capsid in the Resistance to UV-C Radiations

Incidence of Phage Capsid Organization on the Resistance to High Energy Proton Beams

Contact Info

Product

Resources

About