title: The Differential Profiling of Ubiquitin-Proteasome and Autophagy Systems in Different Tissues before the Onset of Huntington's Disease Models.
abstract: Huntington's disease (HD) is a genetic and neurodegenerative disease, leading to motor and cognitive dysfunction in HD patients. At cellular level, this disease is caused by the accumulation of mutant huntingtin (HTT) in different cells, and finally results in the dysfunction of different cells. To clean these mutant proteins, ubiquitin-proteasome system (UPS) and autophagy system are two critical pathways in the brain; however, little is known in other peripheral tissues. As mutant HTT affects different tissues progressively and might influence the UPS and autophagy pathways at early stages, we attempted to examine two clearance systems in HD models before the onset. Here, in vitro results showed that the accumulation of UPS signals with time was observed obviously in neuroblastoma and kidney cells, not in other cells. In HD transgenic mice, we observed the impairment of UPS, but not autophagy, over time in the cortex and striatum. In heart and muscle tissues, disturbance of autophagy was observed, whereas dysfunction of UPS was displayed in liver and lung. These results suggest that two protein clearance pathways are disturbed differentially in different tissues before the onset of HD, and enhancement of protein clearance at early stages might provide a potential stratagem to alleviate the progression of HD.
authors.affiliation: Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Lu-Shiun
authors.initials: LS
authors.lastname: Her
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jian-Yu
authors.initials: JY
authors.lastname: Lin
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Mu-Hui
authors.initials: MH
authors.lastname: Fu
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Chang
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Li
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Tang
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Jhang
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chih-Yi
authors.initials: CY
authors.lastname: Chang
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Meng-Chi
authors.initials: MC
authors.lastname: Shih
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Pei-Hsun
authors.initials: PH
authors.lastname: Cheng
authors.affiliation: Department of Physiology, National Cheng Kung University, Tainan, Taiwan.|Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shang-Hsun
authors.initials: SH
authors.lastname: Yang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D025801:Ubiquitin; D049452:Green Fluorescent Proteins; D046988:Proteasome Endopeptidase Complex
keywords: Huntington's disease (HD); autophagy; protein clearance; transgenic mice; ubiquitin-proteasome system