Volume 13 Issue 1 - 2021
Downregulation of WWOX and Inhibitory GABAergic Interneurons Correlates with Brain Inflammation During Progression of Alzheimer’s Disease
Nan-Shan Chang1,2,3*
1Institute of Molecular Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
2Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA
3Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan, ROC
*Corresponding Author: Nan-Shan Chang, Institute of Molecular Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
Received: December 14, 2020; Published: December 28, 2020


WWOX gene is one of the risk factors for Alzheimer’s disease (AD). Two modes of WWOX action is suggested to account for its association with AD. First, downregulation of WWOX protein in the hippocampus in middle ages may initiate slow aggregation of a protein cascade that ultimately results in increased accumulation of extracellular amyloid beta plaques and intracellular tau tangles, along with reduction of inhibitory GABAergic interneurons, in the brain of patients greater than 70 years old. Second, when proapoptotic pY33-WWOX is converted to pS14-WWOX, pS14-WWOX promotes neuronal degeneration as evidenced by the increased accumulation of the Ser14-phosphorylated form in the brain lesions. Suppression of Ser14 phosphorylation by a small peptide Zfra leads to enhanced protein degradation, reduction in NF-B-mediated inflammation, and restoration of memory loss in triple transgenic mice for AD. In light of the promising findings, Zfra peptide is now on the road to preclinical and clinical trials.

Keywords: WWOX; Neurodegeneration; Alzheimer’s Disease; Risk Factor; Tumor Suppressor


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Citation: Nan-Shan Chang. “Downregulation of WWOX and Inhibitory GABAergic Interneurons Correlates with Brain Inflammation During Progression of Alzheimer’s Disease”. EC Neurology 13.1 (2021): 08-11.

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