title: Tetranectin gene deletion induces Parkinson's disease by enhancing neuronal apoptosis.
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.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Chen
authors.forename: Ersong
authors.initials: E
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Jue
authors.initials: J
authors.lastname: Jiang
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D017353:Gene Deletion; D037181:Lectins, C-Type / Q000235:genetics*; D051379:Mice; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation
chemical_list: D037181:Lectins, C-Type; D034741:RNA, Small Interfering; C048648:tetranectin