The Differential Profiling of Ubiquitin-Proteasome and Autophagy Systems in Different Tissues before the Onset of Huntington's Disease Models

Lu Shiun Her, Jian Yu Lin, Mu Hui Fu, Yu Fan Chang, Chia Ling Li, Ting Yu Tang, Yu Ling Jhang, Chih Yi Chang, Meng Chi Shih, Pei Hsun Cheng, Shang Hsun Yang

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)481-490
Number of pages10
JournalBrain Pathology
Volume25
Issue number4
DOIs
Publication statusPublished - 2015 Jul 1

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

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