Feasibility of β-sheet breaker peptide-H102 treatment for Alzheimer's disease based on β-amyloid hypothesis

• Published in: PloS one 2014-11, Vol.9 (11), p.e112052
• Main Authors: Lin, Lai-xiang, Bo, Xiang-yu, Tan, Yuan-zhen, Sun, Feng-xian, Song, Ming, Zhao, Juan, Ma, Zhi-hong, Li, Mei, Zheng, Kai-jun, Xu, Shu-Mei
• Format: Article
• Language: English
• Subjects: Agglomeration; Alzheimer Disease - drug therapy; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amino acids; Amyloid beta-Protein Precursor - biosynthesis; Amyloid beta-Protein Precursor - genetics; Amyloid precursor protein; Animal cognition; Animals; Apoptosis; Biology and Life Sciences; Brain research; Cognitive ability; Cytokines; Etiology; Feasibility; Feasibility studies; Free radicals; Humans; Hypotheses; Inflammation; Kinases; Laboratory animals; Lipids; Medical treatment; Medicine and Health Sciences; Mice; Mice, Transgenic; Models, Biological; Nervous system; Neurodegenerative diseases; Neurosciences; Neurotoxicity; Pathogenesis; Peptides; Peptides - chemistry; Peptides - genetics; Peptides - pharmacology; Phosphorylation; Physiology; Protein folding; Protein Structure, Secondary; Proteins; Rodents; Tau protein; Transgenic animals; Transgenic mice; β-Amyloid
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0112052

β-amyloid hypothesis is the predominant hypothesis in the study of pathogenesis of Alzheimer's disease. This hypothesis claims that aggregation and neurotoxic effects of amyloid β (Aβ) is the common pathway in a variety of etiological factors for Alzheimer's disease. Aβ peptide derives from amyloid precursor protein (APP). β-sheet breaker peptides can directly prevent and reverse protein misfolding and aggregation in conformational disorders. Based on the stereochemical structure of Aβ1-42 and aggregation character, we had designed a series of β-sheet breaker peptides in our previous work and screened out a 10-residue peptide β-sheet breaker peptide, H102. We evaluated the effects of H102 on expression of P-tau, several associated proteins, inflammatory factors and apoptosis factors, and examined the cognitive ability of APP transgenic mice by behavioral test. This study aims to validate the β-amyloid hypothesis and provide an experimental evidence for the feasibility of H102 treatment for Alzheimer's disease.