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

被引:6
作者
Wang, Xu [1 ]
Yang, Yi [1 ]
Jia, Mingyue [1 ]
Ma, Chi [2 ]
Wang, Mingyu [1 ]
Che, Lihe [3 ]
Yang, Yu [1 ]
Wu, Jiang [1 ]
机构
[1] Jilin Univ, Hosp 1, Dept Neurol, Changchun 130021, Jilin Province, Peoples R China
[2] Jilin Univ, Hosp 1, Dept Neurosurg, Changchun 130021, Jilin Province, Peoples R China
[3] Jilin Univ, Hosp 1, Dept Infect, Changchun 130021, Jilin Province, Peoples R China
基金
中国国家自然科学基金;
关键词
neural regeneration; neurodegenerative disease; gene therapy; Alzheimer's disease; aptamer; amyloid beta peptide; amyloid beta peptide binding alcohol dehydrogenase; decoy peptide; thioredoxin; mitochondrial dysfunction; molecular cloning; grants-supported paper; photographs-containing paper; neuroregeneration; INDUCED MITOCHONDRIAL DYSFUNCTION; ALZHEIMERS-DISEASE; A-BETA; MOUSE MODEL; NEURODEGENERATIVE DISEASES; OXIDATIVE STRESS; TRANSGENIC MICE; ACCUMULATION; ABAD; PROTEIN;
D O I
10.3969/j.issn.1673-5374.2013.01.005
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Amyloid beta peptide binding alcohol dehydrogenase (ABAD) decoy peptide (DP) can competitively antagonize binding of amyloid beta peptide to ABAD and inhibit the cytotoxic effects of amyloid beta 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 beta peptide in NIH-3T3 cells, indicating that the TRX1-ABAD-DP-TRX2 aptamer can bind amyloid beta peptide within cells. In addition, cell morphology and MU results suggested that TRX1-ABAD-DP-TRX2 attenuated amyloid beta 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 beta peptide.
引用
收藏
页码:39 / 48
页数:10
相关论文
共 49 条
[11]   Intraneuronal Aβ42 accumulation in human brain [J].
Gouras, GK ;
Tsai, J ;
Naslund, J ;
Vincent, B ;
Edgar, M ;
Checler, F ;
Greenfield, JP ;
Haroutunian, V ;
Buxbaum, JD ;
Xu, HX ;
Greengard, P ;
Relkin, NR .
AMERICAN JOURNAL OF PATHOLOGY, 2000, 156 (01) :15-20
[12]   Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer's disease [J].
Gouras, Gunnar K. ;
Tampellini, Davide ;
Takahashi, Reisuke H. ;
Capetillo-Zarate, Estibaliz .
ACTA NEUROPATHOLOGICA, 2010, 119 (05) :523-541
[13]   Alzheimer's Disease, Oestrogen and Mitochondria: an Ambiguous Relationship [J].
Grimm, Amandine ;
Lim, Yun-An ;
Mensah-Nyagan, Ayikoe Guy ;
Goetz, Juergen ;
Eckert, Anne .
MOLECULAR NEUROBIOLOGY, 2012, 46 (01) :151-160
[14]   ALZHEIMERS-DISEASE - THE AMYLOID CASCADE HYPOTHESIS [J].
HARDY, JA ;
HIGGINS, GA .
SCIENCE, 1992, 256 (5054) :184-185
[15]   Mitochondrial Dysfunction in Neurodegenerative Diseases [J].
Johri, Ashu ;
Beal, M. Flint .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2012, 342 (03) :619-630
[16]  
Kang KN, ADV BIOCH E IN PRESS
[17]   Intracellular amyloid-β in Alzheimer's disease [J].
LaFerla, Frank M. ;
Green, Kim N. ;
Oddo, Salvatore .
NATURE REVIEWS NEUROSCIENCE, 2007, 8 (07) :499-509
[18]   Peptide Aptamers with Biological and Therapeutic Applications [J].
Li, J. ;
Tan, S. ;
Chen, X. ;
Zhang, C-Y ;
Zhang, Y. .
CURRENT MEDICINAL CHEMISTRY, 2011, 18 (27) :4215-4222
[19]   Inhibition of the Mitochondrial Enzyme ABAD Restores the Amyloid-β-Mediated Deregulation of Estradiol [J].
Lim, Yun-An ;
Grimm, Amandine ;
Giese, Maria ;
Mensah-Nyagan, Ayikoe Guy ;
Villafranca, J. Ernest ;
Ittner, Lars M. ;
Eckert, Anne ;
Goetz, Juergen .
PLOS ONE, 2011, 6 (12)
[20]   Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases [J].
Lin, Michael T. ;
Beal, M. Flint .
NATURE, 2006, 443 (7113) :787-795