WW domain-containing oxidoreductase in neuronal injury and neurological diseases
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// Hsin-Tzu Chang 1 , Chan-Chuan Liu 1 , Shur-Tzu Chen 1 , Ye Vone Yap 2 , Nan-Shang Chang 2,3 and Chun-I Sze 1 1 Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan 2 Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan 3 Advanced Optoelectronic Technology Center, National Cheng Kung University, Tainan, Taiwan Correspondence: Nan-Shan Chang, email: // Chun-I Sze, email: // Keywords : WWOX, WOX1, neurodegeneration, neurites, neuronal death, transcription factors Received : November 14, 2014 Accepted : December 09, 2014 Published : December 10, 2014 Abstract The human and mouse WWOX/Wwox gene encodes a candidate tumor suppressor WW domain-containing oxidoreductase protein. This gene is located on a common fragile site FRA16D . WWOX participates in a variety of cellular events and acts as a transducer in the many signal pathways, including TNF, chemotherapeutic drugs, UV irradiation, Wnt, TGF-β, C1q, Hyal-2, sex steroid hormones, and others. While transiently overexpressed WWOX restricts relocation of transcription factors to the nucleus for suppressing cancer survival, physiological relevance of this regard in vivo has not been confirmed. Unlike many tumor suppressor genes, mutation of WWOX is rare, raising a question whether WWOX is a driver for cancer initiation. WWOX/Wwox was initially shown to play a crucial role in neural development and in the pathogenesis of Alzheimer’s disease and neuronal injury. Later on, WWOX/Wwox was shown to participate in the development of epilepsy, mental retardation, and brain developmental defects in mice, rats and humans. Up to date, most of the research and review articles have focused on the involvement of WWOX in cancer. Here, we review the role of WWOX in neural injury and neurological diseases, and provide perspectives for the WWOX-regulated neurodegeneration.
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WWOX has been implicated in several neurological phenotypes; it binds tau and may play a critical role in regulating tau hyper-phosphorylation, neurofibrillary formation and Aβ aggregation.
“WWOX has been implicated in several neurological phenotypes96; in addition, it binds tau and may play a critical role in regulating tau hyper-phosphorylation, neurofibrillary formation and Aβ aggregation28,29.”
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 [96]
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Alzheimer Disease Genetics Consortium (ADGC), Kunkle, B. W., The European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, P. A. E. R. F. A. D. C. (., Grenier-Boley, B., Sims, R., Bis, J. C., Damotte, V., Naj, A. C., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0358-2 · Cited by 2,946 · see citing works
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- Authors
- Chang, H.-T., Liu, C.-C., Chen, S.-T., Yap, Y. V., Chang, N.-S., & Sze, C.-I.
- Affiliations
- National Cheng Kung University (TW)
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2014-12-10
- Volume
- 5
- Issue
- 23
- Pages
- 11792-11799
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC4322972
- OpenAlex
- W1533927757
- Cited by
- 41
- References
- 54
- Citations by year
- 2023: 2 · 2022: 4 · 2021: 5 · 2020: 1 · 2019: 7 · 2018: 7 · 2017: 3 · 2016: 6 · 2015: 6
- FWCI
- 0.47
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (W81XWH-08–1-0682, W81XWH)
- National Science Council
- National Health Research Institutes (NHRI-EX102)
- National Cheng Kung University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- WWOX, WOX1, neurodegeneration, neuronal injury, neurological disorders, Alzheimer's disease, epilepsy, intellectual disability, brain development, tumor suppressor, transcription factors
- MeSH terms
- WW Domain-Containing Oxidoreductase, Animals, Humans, Nervous System Diseases, Oxidoreductases, Tumor Suppressor Proteins, Mice
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