title: WW domain-containing oxidoreductase in neuronal injury and neurological diseases.
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.
authors.affiliation: Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Hsin-Tzu
authors.initials: HT
authors.lastname: Chang
authors.affiliation: Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chan-Chuan
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shur-Tzu
authors.initials: ST
authors.lastname: Chen
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ye Vone
authors.initials: YV
authors.lastname: Yap
authors.affiliation: Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Advanced Optoelectronic Technology Center, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Nan-Shang
authors.initials: NS
authors.lastname: Chang
authors.affiliation: Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chun-I
authors.initials: CI
authors.lastname: Sze
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D009422:Nervous System Diseases; D010088:Oxidoreductases; D025521:Tumor Suppressor Proteins; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human; C428130:Wwox protein, mouse