Single chain Fv antibodies against the 25-35 Abeta fragment inhibit aggregation and toxicity of Abeta42 |
| |
Authors: | Zameer Andleeb Schulz Philip Wang Min S Sierks Michael R |
| |
Affiliation: | Department of Chemical and Materials Engineering, Arizona State University, Tempe, Arizona 85287-6006, USA. |
| |
Abstract: | Alzheimer's disease (AD) is characterized by the deposition of amyloid-beta (Abeta) protein in the brain. Immunization studies have demonstrated that anti-Abeta antibodies reduce Abeta deposition and improve clinical symptoms seen in AD. However, conventional antibody-based therapies risk an inflammatory response that can result in meningoencephalitis and cerebral hemorrhage. Here we report on the development of human-based single chain variable domain antibody fragments (scFvs) directed against the Abeta 25-35 region as potential therapeutics for AD that do not risk an inflammatory response. The 25-35 region of Abeta represents a promising therapeutic target since it promotes aggregation and is highly toxic. Two scFvs with differing affinities for Abeta were studied, and both inhibited aggregation of Abeta42 as determined by thioflavin T binding assay and atomic force microscopy analysis and blocked Abeta-induced toxicity toward human neuroblastoma SH-SY5Y cells as determined by MTT and LDH release assays. These results provide additional evidence that scFvs against Abeta provide an attractive alternative to more conventional antibody-based therapeutics for controlling aggregation and toxicity of Abeta. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|