WWOX phosphorylation, signaling, and role in neurodegeneration

Chan Chuan Liu, Pei Chuan Ho, I. Ting Lee, Yu An Chen, Chun-Hsien Chu, Chih Chuan Teng, Sheng-Nan Wu, Chun-I Sze, Ming Fu Chiang, Nan-Shan Chang

研究成果: Review article

4 引文 (Scopus)

摘要

Homozygous null mutation of tumor suppressor WWOX/Wwox gene leads to severe neural diseases, metabolic disorders and early death in the newborns of humans, mice and rats. WWOX is frequently downregulated in the hippocampi of patients with Alzheimer's disease (AD). In vitro analysis revealed that knockdown of WWOX protein in neuroblastoma cells results in aggregation of TRAPPC6AΔ, TIAF1, amyloid β, and Tau in a sequential manner. Indeed, TRAPPC6AΔ and TIAF1, but not tau and amyloid β, aggregates are present in the brains of healthy mid-aged individuals. It is reasonable to assume that very slow activation of a protein aggregation cascade starts sequentially with TRAPPC6AΔ and TIAF1 aggregation at mid-ages, then caspase activation and APP de-phosphorylation and degradation, and final accumulation of amyloid β and Tau aggregates in the brains at greater than 70 years old. WWOX binds Tau-hyperphosphorylating enzymes (e.g., GSK-3β) and blocks their functions, thereby supporting neuronal survival and differentiation. As a neuronal protective hormone, 17β-estradiol (E2) binds WWOX at an NSYK motif in the C-terminal SDR (short-chain alcohol dehydrogenase/reductase) domain. In this review, we discuss how WWOX and E2 block protein aggregation during neurodegeneration, and how a 31-amino-acid zinc finger-like Zfra peptide restores memory loss in mice.

原文English
文章編號563
期刊Frontiers in Neuroscience
12
發行號AUG
DOIs
出版狀態Published - 2018 八月 15

指紋

Amyloid
Phosphorylation
Genetic Suppression
Glycogen Synthase Kinase 3
Proteins
Alcohol Dehydrogenase
Zinc Fingers
Metabolic Diseases
Memory Disorders
Brain
Caspases
Neuroblastoma
Estradiol
Hippocampus
Alzheimer Disease
Oxidoreductases
Down-Regulation
Newborn Infant
Hormones
Amino Acids

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

引用此文

Liu, Chan Chuan ; Ho, Pei Chuan ; Lee, I. Ting ; Chen, Yu An ; Chu, Chun-Hsien ; Teng, Chih Chuan ; Wu, Sheng-Nan ; Sze, Chun-I ; Chiang, Ming Fu ; Chang, Nan-Shan. / WWOX phosphorylation, signaling, and role in neurodegeneration. 於: Frontiers in Neuroscience. 2018 ; 卷 12, 編號 AUG.
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abstract = "Homozygous null mutation of tumor suppressor WWOX/Wwox gene leads to severe neural diseases, metabolic disorders and early death in the newborns of humans, mice and rats. WWOX is frequently downregulated in the hippocampi of patients with Alzheimer's disease (AD). In vitro analysis revealed that knockdown of WWOX protein in neuroblastoma cells results in aggregation of TRAPPC6AΔ, TIAF1, amyloid β, and Tau in a sequential manner. Indeed, TRAPPC6AΔ and TIAF1, but not tau and amyloid β, aggregates are present in the brains of healthy mid-aged individuals. It is reasonable to assume that very slow activation of a protein aggregation cascade starts sequentially with TRAPPC6AΔ and TIAF1 aggregation at mid-ages, then caspase activation and APP de-phosphorylation and degradation, and final accumulation of amyloid β and Tau aggregates in the brains at greater than 70 years old. WWOX binds Tau-hyperphosphorylating enzymes (e.g., GSK-3β) and blocks their functions, thereby supporting neuronal survival and differentiation. As a neuronal protective hormone, 17β-estradiol (E2) binds WWOX at an NSYK motif in the C-terminal SDR (short-chain alcohol dehydrogenase/reductase) domain. In this review, we discuss how WWOX and E2 block protein aggregation during neurodegeneration, and how a 31-amino-acid zinc finger-like Zfra peptide restores memory loss in mice.",
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WWOX phosphorylation, signaling, and role in neurodegeneration. / Liu, Chan Chuan; Ho, Pei Chuan; Lee, I. Ting; Chen, Yu An; Chu, Chun-Hsien; Teng, Chih Chuan; Wu, Sheng-Nan; Sze, Chun-I; Chiang, Ming Fu; Chang, Nan-Shan.

於: Frontiers in Neuroscience, 卷 12, 編號 AUG, 563, 15.08.2018.

研究成果: Review article

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AU - Liu, Chan Chuan

AU - Ho, Pei Chuan

AU - Lee, I. Ting

AU - Chen, Yu An

AU - Chu, Chun-Hsien

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AU - Wu, Sheng-Nan

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