A Peptide That Binds Specifically to the β-Amyloid of Alzheimer's Disease: Selection and Assessment of Anti-β-Amyloid Neurotoxic Effects

Abstract

The accumulation of the amyloid-β peptide (Aβ) into amyloid plaques, an essential event in Alzheimer's disease (AD) pathogenesis, has caused researchers to seek compounds that physiologically bind Aβ and modulate its aggregation and neurotoxicity. In order to develop new Aβ-specific peptides for AD, a randomized 12-mer peptide library with Aβ1-10 as the target was used to identify peptides in the present study. After three rounds of selection, specific phages were screened, and their binding affinities to Aβ1-10 were found to be highly specific. Finally, a special peptide was synthesized according to the sequences of the selected phages. In addition, the effects of the special peptide on Aβ aggregation and Aβ-mediated neurotoxicity in vitro and in vivo were assessed. The results show that the special peptide not only inhibited the aggregation of Aβ into plaques, but it also alleviated Aβ-induced PC12 cell viability and apoptosis at appropriate concentrations as assessed by the cell counting kit-8 assay and propidium iodide staining. Moreover, the special peptide exhibited a protective effect against Aβ-induced learning and memory deficits in rats, as determined by the Morris water maze task. In conclusion, we selected a peptide that specifically binds Aβ1-10 and can modulate Aβ aggregation and Aβ-induced neuronal damage. This opens up possibilities for the development of a novel therapeutic approach for the treatment of AD.

Anti-Aggregating Effect of the Naturally Occurring Dipeptide Carnosine on Aβ1-42 Fibril Formation

“…Aβ1-42 stock solution (100 µM) was prepared by dissolving the peptide fragment powder (two different lots from Sigma-Aldrich were used, namely lot n. 079K8729 and SLBC5079V) in sterile Milli-Q water, as previously reported [43], [58], [60]–[65]. Aliquots (5 µl) were lyophilized and stored at −20°C until use.…”

“…Currently, the inhibitory activity of small molecules (small peptides included) able to break down the structural organization of soluble or aggregating Aβ1-42 in the fibrillogenesis process is under investigation [57], [58] with the aim of identifying novel inhibitors of Aβ1-42 aggregation and toxicity, a major topic in AD research [59]. In this context, we considered the direct effects of carnosine, a naturally occurring dipeptide in nervous cells, on the fibrillogenesis process of the Aβ1-42 fragment.…”

Shikonin Protects PC12 Cells Against β-amyloid Peptide-Induced Cell Injury Through Antioxidant and Antiapoptotic Activities

“…In addition, it has been reported that several alternative approaches have preventative effects on the progression of AD, including anti-Aβ antibodies, inhibitors of β- and γ-secretases, antioxidants and anti-inflammatory agents 9 – 12 . However, the stability, validity, cost, safety and development time restrict the use of these treatments for preventing AD 13 . Thus, searching for a safer and more effective drug for the treatment of AD remains an important challenge in drug discovery.…”

Radiation-Guided Peptide Delivery in a Mouse Model of Nasopharyngeal Carcinoma

“…Moreover, they also exhibit accelerated metabolism in the body. Their limitations include instability on the tumor cell surface and alterations according to the environment [ 17 , 18 ]. Sugahara et al found a handful of peptides that could specifically interact with the tumor cell surface, constituting ideal carriers of targeted therapy [ 19 ].…”