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Expression of taurine transporter (TauT) by heat shock factor1 (HSF1) is linked to the pathology of motor neurons in amyotrophic lateral sclerosis (ALS)

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Authors
정민경
Advisor
류훈
Issue Date
2012
Publisher
서울대학교 대학원
Keywords
Taurine transporterHeat shock factor 1transcriptiontaurine uptakeALS
Abstract
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurological disorder characterized by progressive paralysis caused by the degeneration of motor neurons throughout the central nervous system. Mutations of the free radical scavenging enzyme Cu/Zn superoxide dismutase 1 (SOD1) are a cause of familial ALS, but it is still not clear how mutations cause cell death. In the present study, we demonstrated an age-dependent increase in taurine transporter (TauT) immunoreactivity in spinal cord motor neurons of ALS transgenic mice (mutant SOD1 (G93A)) and a similar increase in TauT in spinal motor neurons of patients with ALS. Chromatin immunoprecipitation (ChIP) analysis verified that heat shock factor 1 (HSF1) preferentially occupies HSF1 binding element in the promoter of TauT under oxidative stress conditions as well as in ALS spinal cords. Knockdown of HSF1 by small interfering RNA (siRNA) reduced the transcriptional activity of TauT. Using [3H]-taurine, we confirmed that an elevated expression of TauT directly contributes to increased taurine uptake in ALS motor neurons. In addition, we showed that taurine plays an antioxidant role and may prevent motor neuron loss due to oxidative stress in ALS. Our findings suggest that HSF1-induced TauT expression partially protects motor neurons by compensating for constitutive oxidative stress, which is thought to be a key mechanism contributing to the pathogenesis of ALS. Taken together, our results suggest that TauT is a novel pathological marker for stressed motor neurons in ALS and that modulation of TauT and taurine may slow neuronal degeneration in ALS.
Language
eng
URI
http://hdl.handle.net/10371/171489

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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Theses (Master's Degree_의과학과)
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