The mechanism of interaction between copper transporters and α-synuclein
作者单位：Institute of Neuroscience College of Life and Health Sciences Northeastern University
会议名称：《中国神经科学学会第十二届全国学术会议》
会议日期：2017年
学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
关 键 词：copper Ctr1 a-synuclein PD
摘 要：Previous studies showed that Copper and Copper transport 1（Ctr1） were decreased in the substantia nigra compacta of the midbrain and the striatum of patients with Parkinson’s disease（PD）. Copper is related to increased oxidative stress, α-synuclein oligomerization, and Lewy-body formation. In addition, Copper regulates neurotransmission when it is released after neuronal stimulus and the metal is able to modulate the function of NMDA and GABA receptors. At present, there is limited information about the pathological mechanism of copper and it’s related proteins in PD. Therefore, it is important to study the pathology of copper in PD. The present project aims to investigate the interaction between copper, copper related proteins（Ctr1, CCS, COX4, etc.） and α-synuclein to seek for new therapeutic targets for PD. Using HEK293 or SH-SY5 Y cell lines stably expressing human wildtype α-synuclein tagged with GFP or Ds Red, we detected that copper can promote α-synuclein aggregation in a dosedependent manner. In order to study the role of Ctr1 on α-synuclein accumulation and aggregation and subsequent effects on neuronal function, we have established transgenic mouse model overexpressing Ctr1 and knockout Ctr1 models at specific brain regions, such as the hippocampus and the substantia nigra. Open field test and Morris water maze test showed little changes in the Ctr1 knockout mice in the hippocampus compared to the WT mice. In on-going experiments, we do stereotaxic injection of copper or α-synuclein fibrils to the mice to detect copper concentration, protein expression of copper relative protein and the distribution and expression of α-synuclein.