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Involvement of receptor tyrosine kinase Tyro3 in amyloidogenic APP processing and β-amyloid deposition in Alzheimer's disease models.
PLoS One. 2012; 7(6):e39035.Plos

Abstract

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease known to humankind. It is characterized by brain atrophy, extracellular amyloid plaques, and intracellular neurofibril tangles. β-Amyloid cascade is considered the major causative player in AD. Up until now, the mechanisms underlying the process of Aβ generation and accumulation in the brain have not been well understood. Tyro3 receptor belongs to the TAM receptor subfamily of receptor protein tyrosine kinases (RPTKs). It is specifically expressed in the neurons of the neocortex and hippocampus. In this study, we established a cell model stably expressing APPswe mutants and producing Aβ. We found that overexpression of Tyro3 receptor in the cell model significantly decreased Aβ generation and also down-regulated the expression of β-site amyloid precursor protein cleaving enzyme (BACE1). However, the effects of Tyro3 were inhibited by its natural ligand, Gas6, in a concentration-dependent manner. In order to confirm the role of Tyro3 in the progression of AD development, we generated an AD transgenic mouse model accompanied by Tyro3 knockdown. We observed a significant increase in the number of amyloid plaques in the hippocampus in the mouse model. More plaque-associated clusters of astroglia were also detected. The present study may help researchers determine the role of Tyro3 receptor in the neuropathology of AD.

Authors+Show Affiliations

Department of Physiology, Capital Medical University, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22701746

Citation

Zheng, Yan, et al. "Involvement of Receptor Tyrosine Kinase Tyro3 in Amyloidogenic APP Processing and Β-amyloid Deposition in Alzheimer's Disease Models." PloS One, vol. 7, no. 6, 2012, pp. e39035.
Zheng Y, Wang Q, Xiao B, et al. Involvement of receptor tyrosine kinase Tyro3 in amyloidogenic APP processing and β-amyloid deposition in Alzheimer's disease models. PLoS ONE. 2012;7(6):e39035.
Zheng, Y., Wang, Q., Xiao, B., Lu, Q., Wang, Y., & Wang, X. (2012). Involvement of receptor tyrosine kinase Tyro3 in amyloidogenic APP processing and β-amyloid deposition in Alzheimer's disease models. PloS One, 7(6), e39035. https://doi.org/10.1371/journal.pone.0039035
Zheng Y, et al. Involvement of Receptor Tyrosine Kinase Tyro3 in Amyloidogenic APP Processing and Β-amyloid Deposition in Alzheimer's Disease Models. PLoS ONE. 2012;7(6):e39035. PubMed PMID: 22701746.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of receptor tyrosine kinase Tyro3 in amyloidogenic APP processing and β-amyloid deposition in Alzheimer's disease models. AU - Zheng,Yan, AU - Wang,Qi, AU - Xiao,Bing, AU - Lu,Qingjun, AU - Wang,Yizheng, AU - Wang,Xiaomin, Y1 - 2012/06/11/ PY - 2012/02/07/received PY - 2012/05/15/accepted PY - 2012/6/16/entrez PY - 2012/6/16/pubmed PY - 2012/11/9/medline SP - e39035 EP - e39035 JF - PloS one JO - PLoS ONE VL - 7 IS - 6 N2 - Alzheimer's disease (AD) is the most common progressive neurodegenerative disease known to humankind. It is characterized by brain atrophy, extracellular amyloid plaques, and intracellular neurofibril tangles. β-Amyloid cascade is considered the major causative player in AD. Up until now, the mechanisms underlying the process of Aβ generation and accumulation in the brain have not been well understood. Tyro3 receptor belongs to the TAM receptor subfamily of receptor protein tyrosine kinases (RPTKs). It is specifically expressed in the neurons of the neocortex and hippocampus. In this study, we established a cell model stably expressing APPswe mutants and producing Aβ. We found that overexpression of Tyro3 receptor in the cell model significantly decreased Aβ generation and also down-regulated the expression of β-site amyloid precursor protein cleaving enzyme (BACE1). However, the effects of Tyro3 were inhibited by its natural ligand, Gas6, in a concentration-dependent manner. In order to confirm the role of Tyro3 in the progression of AD development, we generated an AD transgenic mouse model accompanied by Tyro3 knockdown. We observed a significant increase in the number of amyloid plaques in the hippocampus in the mouse model. More plaque-associated clusters of astroglia were also detected. The present study may help researchers determine the role of Tyro3 receptor in the neuropathology of AD. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/22701746/Involvement_of_receptor_tyrosine_kinase_Tyro3_in_amyloidogenic_APP_processing_and_β_amyloid_deposition_in_Alzheimer's_disease_models_ L2 - http://dx.plos.org/10.1371/journal.pone.0039035 DB - PRIME DP - Unbound Medicine ER -