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Updated: Aug 26, 2025
09:22
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
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Aging-associated REGγ proteasome decline predisposes to tauopathy
Jialu Tu1, Haiyang Zhang1, Ting Yang1
1Institute of Biomedical Sciences, Shanghai Key Laboratory of Brain Functional Genomics (Ministry of Education), School of Life Sciences, East China Normal University, Shanghai, China.
The Journal of Biological Chemistry
|October 9, 2022
Summary
Aging-associated decline in the REGγ-20S proteasome impairs tau turnover, contributing to tauopathies. Restoring REGγ levels may prevent neurodegeneration and tauopathy symptoms.
Area of Science:
- Neuroscience
- Molecular Biology
- Aging Research
Background:
- The REGγ-20S proteasome is an ATP- and ubiquitin-independent degradation system.
- Its decline is associated with aging and may influence neurodegenerative diseases like tauopathies.
Purpose of the Study:
- To investigate the role of REGγ in tau turnover and its implications in tauopathy.
- To explore REGγ as a potential therapeutic target for tau-related neurodegenerative diseases.
Main Methods:
- Utilized REGγ knockout (KO) mice, PS19 mice (a tauopathy model), and REGγ overexpression (OE) models.
- Assessed tau accumulation, neurodegeneration, microglial activation, and behavioral abnormalities.
Main Results:
- REGγ deficiency exacerbated tau accumulation, neurodegeneration, and behavioral deficits in tauopathy models.
- REGγ overexpression alleviated tauopathy symptoms and protected against neuronal loss.
Conclusions:
- REGγ plays a critical role in degrading tau, including toxic phosphorylated and oligomeric forms.
- Maintaining REGγ levels is crucial for preventing tauopathy progression and associated neurodegeneration.
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