Diaminodiphenyl sulfone–induced parkin ameliorates age-dependent dopaminergic neuronal loss
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.
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These signals plus subthreshold common variant associations account for about 31% of the genetic variance of LOAD.
“These signals, combined with ‘subthreshold’ common variant associations, account for ~31% of the genetic variance of LOAD2”
From Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (2019) · cites this paper as [2]
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- Authors
- Lee, Y.-I., Kang, H., Ha, Y. W., Chang, K.-Y., Cho, S.-C., Song, S. O., Kim, H., Jo, A., Khang, R., Choi, J.-Y., Lee, Y., Park, S. C., & Shin, J.-H.
- Affiliations
- Daegu Gyeongbuk Institute of Science and Technology (KR)
- Samsung Biomedical Research Institute (KR)
- Samsung (South Korea) (KR)
- Corresponding author
- Shin, Joo-Ho
- ORCID
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 41
- Pages
- 1-10
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2175467017
- Cited by
- 16
- References
- 43
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 3
- FWCI
- 1.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NRF (NRF-2012R1A1A1012435)
- Ministry of Science, ICT and Future Planning
- Samsung Biomedical Research Institute (SMX1132521)
- Samsung Advanced Institute of Technology
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- dapsone, Parkin, dopaminergic neuron loss, Parkinson's disease, age-related neurodegeneration, substantia nigra, neuroprotection, MPP+, MPTP, ATF4, PERK signaling, SH-SY5Y cells, oxidative stress
- MeSH terms
- Aging, Animals, Anti-Inflammatory Agents, Brain, Cells, Cultured, Dapsone, Disease Models, Animal, Female, Male, Mice, Inbred C57BL, Parkinson Disease, Substantia Nigra, Signal Transduction, Neuroprotective Agents, eIF-2 Kinase, Ubiquitin-Protein Ligases, Activating Transcription Factor 4, Dopaminergic Neurons, Endoplasmic Reticulum Stress
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