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

Abstract

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.

A Novel Serum‐Based Diagnosis of Alzheimer's Disease Using an Advanced Phage‐Based Biochip

“…[15] These libraries have been often used for screening disease-specific antigen mimics, including A𝛽 autoantibodies. [16][17][18] In this work, we used six phages, each expressing a unique small peptide on its surface, which recognize conformation-specific IgG1 A𝛽 autoantibodies, to determine if they could be used to discriminate between different stages of AD based on the amount of A𝛽 autoantibodies in the sera.…”

Synergistic Screening of Peptide-Based Biotechnological Drug Candidates for Neurodegenerative Diseases using Yeast Display and Phage Display

“…; https://doi.org/10.1101/2023.04.14.536742 doi: bioRxiv preprint up to 10 10 peptide sequences on the coat of the phage, phage display libraries have a wide range of applications, such as the discovery of peptides targeting specific tissues, organs, or tumors, molecular imaging, diagnosis and therapies for neurological disorders, epitope mapping, and novel antibody discoveries, etc. [11][12][13][14][15][16][17][18] . The versatility of peptide screening provides a significant opportunity to select high-affinity bioactive peptides against specific targets 19 .…”

Astragalus mongholicus Bunge (Fabaceae): Bioactive Compounds and Potential Therapeutic Mechanisms Against Alzheimer’s Disease

“…According to statistics from Alzheimer’s Disease International, Worldwide there are over 50 million people suffering from dementia in 2018, and 152 million by 2050. Among them, approximately 60–70% are inflicted by AD ( Zhang et al, 2022 ). As the aging population increases, AD poses a great challenge to the society in terms of medical resources and economic burden ( Alzheimer’s Association, 2020 ).…”