The novel amyloid-beta peptide aptamer inhibits intracellular amyloid-beta peptide toxicity

Xu Wang; Yi Yang; Mingyue Jia; Chi Ma; Mingyu Wang; Lihe Che; Yu Yang; Jiang Wu

doi:10.3969/j.issn.1673-5374.2013.01.005

The novel amyloid-beta peptide aptamer inhibits intracellular amyloid-beta peptide toxicity

Neural Regen Res. 2013 Jan 5;8(1):39-48. doi: 10.3969/j.issn.1673-5374.2013.01.005.

Authors

Xu Wang¹, Yi Yang¹, Mingyue Jia¹, Chi Ma², Mingyu Wang¹, Lihe Che³, Yu Yang¹, Jiang Wu¹

Affiliations

¹ Department of Neurology, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
² Department of Neurosurgery, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.
³ Department of Infection, First Hospital of Jilin University, Changchun 130021, Jilin Province, China.

PMID: 25206370
PMCID: PMC4107502
DOI: 10.3969/j.issn.1673-5374.2013.01.005

Abstract

Amyloid β peptide binding alcohol dehydrogenase (ABAD) decoy peptide (DP) can competitively antagonize binding of amyloid β peptide to ABAD and inhibit the cytotoxic effects of amyloid β peptide. Based on peptide aptamers, the present study inserted ABAD-DP into the disulfide bond of human thioredoxin (TRX) using molecular cloning technique to construct a fusion gene that can express the TRX1-ABAD-DP-TRX2 aptamer. Moreover, adeno-associated virus was used to allow its stable expression. Immunofluorescent staining revealed the co-expression of the transduced fusion gene TRX1-ABAD-DP-TRX2 and amyloid β peptide in NIH-3T3 cells, indicating that the TRX1-ABAD-DP-TRX2 aptamer can bind amyloid β peptide within cells. In addition, cell morphology and MTT results suggested that TRX1-ABAD-DP-TRX2 attenuated amyloid β peptide-induced SH-SY5Y cell injury and improved cell viability. These findings confirmed the possibility of constructing TRX-based peptide aptamer using ABAD-DP. Moreover, TRX1-ABAD-DP-TRX2 inhibited the cytotoxic effect of amyloid β peptide.

Keywords: Alzheimer's disease; amyloid β peptide; amyloid β peptide binding alcohol dehydrogenase; aptamer; decoy peptide; gene therapy; grants-supported paper; mitochondrial dysfunction; molecular cloning; neural regeneration; neurodegenerative disease; neuroregeneration; photographs-containing paper; thioredoxin.