Reviews: Gerotarget (Focus on Aging):

WW domain-containing oxidoreductase in neuronal injury and neurological diseases

Hsin-Tzu Chang, Chan-Chuan Liu, Shur-Tzu Chen, Ye Vone Yap, Nan-Shang Chang _ and Chun-I Sze

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Oncotarget. 2014; 5:11792-11799. https://doi.org/10.18632/oncotarget.2961

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Hsin-Tzu Chang1, Chan-Chuan Liu1, Shur-Tzu Chen1, Ye Vone Yap2, Nan-Shang Chang2,3 and Chun-I Sze1

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


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


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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