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Diaminodiphenyl sulfone-induced parkin ameliorates age-dependent dopaminergic neuronal loss

Title
Diaminodiphenyl sulfone-induced parkin ameliorates age-dependent dopaminergic neuronal loss
Author(s)
Lee, Yun IlKang, Ho JinHa, Young WanChang, Ki YoungCho, Sung ChunSong, Sang OkKim, Hye InJo, A ReumKhang, RinChoi, Jeong YunLee, Yun JongPark, Sang ChulShin, Joo Ho
Issued Date
2016
Citation
Neurobiology of Aging, v.41, pp.1 - 10
Type
Article
ISSN
0197-4580
Abstract
During normal aging, the number of dopaminergic (DA) neurons in the substantia nigra progressively diminishes, although massive DA neuronal loss is a hallmark sign of Parkinson's disease. Unfortunately, there is little known about the molecular events involved in age-related DA neuronal loss. In this study, we found that (1) the level of parkin was decreased in the cerebellum, brain stem, substantia nigra, and striatum of aged mice, (2) diaminodiphenyl sulfone (DDS) restored the level of parkin, (3) DDS prevented age-dependent DA neuronal loss, and (4) DDS protected SH-SY5Y cells from 1-methyl-4-phenylpyridinium and hydrogen peroxide. Furthermore, pretreatment and/or post-treatment of DDS in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease model attenuated DA neuronal loss and restored motor behavior. DDS transcriptionally activated parkin via protein kinase RNA-like endoplasmic reticulum kinase-activating transcription factor 4 signaling and DDS not only failed to induce parkin expression but also failed to rescue SH-SY5Y cells from 1-methyl-4-phenylpyridinium in the absence of ATF4. Herein, we demonstrated for the first time that DDS increased parkin level and served as a neuroprotective agent for age-dependent DA neuronal loss. Thus, DDS may be a potential therapeutic agent for age-related neurodegeneration. © 2016 Elsevier Inc.
URI
http://hdl.handle.net/20.500.11750/2761
DOI
10.1016/j.neurobiolaging.2015.11.008
Publisher
Elsevier Inc.
Related Researcher
  • 이윤일 Lee, Yun-Il
  • Research Interests Aging; 노화; Aging-related diseases; 노인성 질환; Parkinson's disease; 파킨슨병; Sarcopenia; 근감소증; Demyelinating disease; 탈수초화 질환
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Appears in Collections:
Division of Biomedical Technology 1. Journal Articles

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