U.S. flag

An official website of the United States government

Dot gov

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Https

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

PubAg

Main content area

Tetranectin gene deletion induces Parkinson's disease by enhancing neuronal apoptosis

Author:
Zhifeng Chen, Ersong Wang, Rong Hu, Yu Sun, Lei Zhang, Jue Jiang, Ying Zhang, Hong Jiang
Source:
Biochemical and biophysical research communications 2015 v.468 pp. 400-407
ISSN:
0006-291X
Subject:
Parkinson disease, animal models, apoptosis, biomarkers, caspase-3, cell culture, cell viability, cerebrospinal fluid, gene deletion, mice, neurons, patients, small interfering RNA, transgenic animals, tyrosine 3-monooxygenase
Abstract:
Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). We previously identified tetranectin (TET) as a potential biomarker for PD whose expression is downregulated in the cerebrospinal fluid of PD patients. In the present study, we investigate the role of TET in neurodegeneration in vitro and in vivo. Our results showed that siRNA knockdown of TET decreased cell viability and the number of tyrosine hydroxylase (TH) positive cells, whereas it increased caspase-3 activity and the Bax/Bcl-2 ratio in cultured primary dopaminergic neurons. Overexpression of TET protected dopaminergic neurons against neuronal apoptosis in 1-methyl-4-phenylpyridinium cell culture model in vitro. In TET knockdown mouse model of PD, TET gene deletion decreased the number of TH positive cells in the SNpc, induced apoptosis via the p53/Bax pathway, and significantly impaired the motor behavior of transgenic mice. The findings suggest that TET plays a neuroprotective role via reducing neuron apoptosis and could be a valuable biomarker or potential therapeutic target for the treatment of patients with PD.
Agid:
5332758