Alzheimer's disease (AD) is a neurodegenerative disorder for which there is no cure or effective treatment. One of the major neuropathological signatures of AD is the deposition of amyloid plaques in the brain of affected people. Although the role of these structures in the pathogenesis of the disease is not fully understood, recent findings have provided evidence that amyloid may be a key player in the disease. Therefore, preventing and reversing cerebral amyloid deposition have become an attractive therapeutic strategy for AD. We have engineered synthetic beta-sheet breaker peptides to bind soluble amyloid peptide and prevent and reverse its conversion to the beta-sheet rich aggregated structure, precursor of the amyloid plaques. Results in vitro, in cell culture and in vivo suggest that beta-sheet breaker peptides might be candidates for an AD-therapy focused to reduce amyloid deposition.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/978-3-7091-6139-5_27 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Discovering Effective Chiral Dipeptides against Aβ(1-42) Aggregation by the Computational Screening Strategy.
ACS Chem Neurosci
October 2024
State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P. R. China.
Article Synopsis
- Researchers studied β-sheet-breaker (BSB) peptides to inhibit amyloidogenic aggregation linked to Alzheimer's, focusing on dipeptides.
- They developed a computational screening method to analyze all chiral dipeptide sequences and identified the WP dipeptide which effectively inhibited Aβ(1-42) aggregation.
- The study showed that WP works by forming hydrophobic contacts and hydrogen bonds with Aβ, disrupting aggregation processes, indicating its potential as a therapeutic agent for Alzheimer's disease.
Synthesis, biological evaluation and metadynamics simulations of novel -methyl β-sheet breaker peptides as inhibitors of Alzheimer's β-amyloid fibrillogenesis.
RSC Med Chem
July 2024
Department of Chemical Sciences, University of Napoli Federico II Via Cintia 4 I-80126 Napoli Italy.
Several scientific evidences report that a central role in the pathogenesis of Alzheimer's disease is played by the deposition of insoluble aggregates of β-amyloid proteins in the brain. Because Aβ is self-assembling, one possible design strategy is to inhibit the aggregation of Aβ peptides using short peptide fragments homologous to the full-length wild-type Aβ protein. In the past years, several studies have reported on the synthesis of some short synthetic peptides called β-sheet breaker peptides (BSBPs).
View Article and Find Full Text PDFHydrophobic C-Terminal Peptide Analog Aβ Protects the Neurons from Aβ-Induced Toxicity.
ACS Chem Neurosci
June 2024
Department of Bioscience & Bioengineering, Indian Institute of Technology, Jodhpur, NH 65, Surpura Bypass Road, Karwar, Jodhpur, Rajasthan 342037, India.
Spontaneous aggregation of amyloid beta (Aβ) leads to the formation of neurotoxic senile plaque considered as the most crucial event in Alzheimer's disease (AD) progression. Inhibition or disruption of this deadly aggregate formation is one of the most efficient strategies for the development of potential therapeutics, and extensive research is in progress by various research groups. In this direction, the development of a peptide analogous to that of the native Aβ peptide is an attractive strategy.
View Article and Find Full Text PDFDefensin-based therapeutic peptide design in attenuating V30M TTR-induced Familial Amyloid Polyneuropathy.
3 Biotech
July 2023
Quantitative Biology Lab, Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology (VIT, Deemed to Be University), Vellore, Tamil Nadu 632014 India.
Unlabelled: In the present study, we aimed to formulate an effective therapeutic candidate against V30M mutant transthyretin (TTR) protein to hinder its pathogenic misfolding. Nicotiana alata Defensin 1 (NaD1) Antimicrobial Peptide (AMP) was availed due to its tendency to aggregate, which may compete for aggregation-prone regions of pathogenic TTR protein. Based on NaD1's potential to bind to V30M TTR, we proposed NaD1-derived tetra peptides: CKTE and SKIL to be initial therapeutic candidates.
View Article and Find Full Text PDFDesign and synthesis of multi-functional small-molecule based inhibitors of amyloid-β aggregation: Molecular modeling and in vitro evaluation.
PLoS One
May 2023
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Amyloid-β1-42 (Aβ42) peptide aggregate formation in the brain plays a crucial role in the onset and progression of Alzheimer's disease. According to published research, the Aβ monomer's amino acid residues KLVFF (16-20) self-associate to create antiparallel β-sheet fibrils. Small compounds can prevent self-assembly and destroy Aβ fibrils by attaching to the Aβ16-20 regions of Aβ42.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!