Mechanism of Tau Hyperphosphorylation Involving Lysosomal Enzyme Asparagine Endopeptidase in a Mouse Model of Brain Ischemia

2018 ◽  
Vol 63 (2) ◽  
pp. 821-833 ◽  
Author(s):  
Gustavo Basurto-Islas ◽  
Jin-hua Gu ◽  
Yunn Chyn Tung ◽  
Fei Liu ◽  
Khalid Iqbal
Keyword(s):  
Mouse Model ◽  
Brain Ischemia ◽  
Lysosomal Enzyme ◽  
Tau Hyperphosphorylation

scholarly journals UBE4B, a microRNA-9 target gene, promotes autophagy-mediated Tau degradation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Manivannan Subramanian ◽  
Seung Jae Hyeon ◽  
Tanuza Das ◽  
Yoon Seok Suh ◽  
Yun Kyung Kim ◽  
...  
Keyword(s):  
Mouse Model ◽  
Ubiquitin Ligase ◽  
Therapeutic Approach ◽  
Target Gene ◽  
Neuroblastoma Cells ◽  
E3 Ligase ◽  
Tau Hyperphosphorylation ◽  
Phosphorylated Tau ◽  
Major Pathway ◽  
The Brain

AbstractThe formation of hyperphosphorylated intracellular Tau tangles in the brain is a hallmark of Alzheimer’s disease (AD). Tau hyperphosphorylation destabilizes microtubules, promoting neurodegeneration in AD patients. To identify suppressors of tau-mediated AD, we perform a screen using a microRNA (miR) library in Drosophila and identify the miR-9 family as suppressors of human tau overexpression phenotypes. CG11070, a miR-9a target gene, and its mammalian orthologue UBE4B, an E3/E4 ubiquitin ligase, alleviate eye neurodegeneration, synaptic bouton defects, and crawling phenotypes in Drosophila human tau overexpression models. Total and phosphorylated Tau levels also decrease upon CG11070 or UBE4B overexpression. In mammalian neuroblastoma cells, overexpression of UBE4B and STUB1, which encodes the E3 ligase CHIP, increases the ubiquitination and degradation of Tau. In the Tau-BiFC mouse model, UBE4B and STUB1 overexpression also increase oligomeric Tau degradation. Inhibitor assays of the autophagy and proteasome systems reveal that the autophagy-lysosome system is the major pathway for Tau degradation in this context. These results demonstrate that UBE4B, a miR-9 target gene, promotes autophagy-mediated Tau degradation together with STUB1, and is thus an innovative therapeutic approach for AD.

Altered phosphorylation but no neurodegeneration in a mouse model of tau hyperphosphorylation

2011 ◽  
Vol 32 (6) ◽  
pp. 991-1006 ◽  
Author(s):  
M. Hundelt ◽  
T. Fath ◽  
K. Selle ◽  
K. Oesterwind ◽  
J. Jordan ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tau Hyperphosphorylation

NAD+ administration decreases ischemic brain damage partially by blocking autophagy in a mouse model of brain ischemia

2012 ◽  
Vol 512 (2) ◽  
pp. 67-71 ◽  
Author(s):  
Chaobo Zheng ◽  
Jin Han ◽  
Weiliang Xia ◽  
Shengtao Shi ◽  
Jianrong Liu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Brain Damage ◽  
Brain Ischemia ◽  
Ischemic Brain Damage ◽  
Ischemic Brain

The hunt for a cure for Alzheimer’s disease receives a timely boost

2019 ◽  
Vol 11 (509) ◽  
pp. eaaz0311
Author(s):  
Vikramaditya G. Yadav
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Therapeutic Strategy ◽  
Glutamate Uptake ◽  
Tau Hyperphosphorylation ◽  
Better Than

Therapeutic strategy based on inhibition of tau hyperphosphorylation performs better than glutamate uptake by astrocytes in a mouse model.

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