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Updated: Jul 27, 2025
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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
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Mutant Tau protein-induced abnormalities in the Na
Marta Sidoryk-Węgrzynowicz1, Beata Dąbrowska-Bouta1, Grzegorz Sulkowski1
1Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 Pawińskiego str, 02-106, Warsaw, Poland.
Neurochemistry International
|June 9, 2023
Summary
Mutant Tau protein causes neuronal damage and disrupts the glutamate-glutamine cycle (GGC) in brain cells. Astrocytes protect neurons by restoring glutamine transport, highlighting their role in Tau pathology.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Tau pathology is linked to neurodegeneration and astrogliosis in diseases like tauopathy.
- Astrocytes play a crucial role in maintaining neuronal integrity, particularly through the glutamate-glutamine cycle (GGC).
- Dysfunction in the GGC is implicated in the progression of neurodegenerative disorders.
Purpose of the Study:
- To investigate the functional impact of Tau pathology on key components of the GGC in an in vitro model.
- To elucidate the role of astrocytes in modulating Tau-induced neuronal damage via the GGC.
- To identify specific alterations in glutamine transport mechanisms affected by mutant Tau.
Main Methods:
- Utilized an in vitro model with neuronal cultures exposed to mutant recombinant Tau (rTau) with or without astrocyte-conditioned medium (ACM).
- Assessed neuronal degeneration and changes in microtubule-associated protein 2 (MAP2) expression.
- Quantified glutamine (Gln) uptake in neurons and astrocytes using radiolabeled tracers to analyze specific transporter systems.
Main Results:
- Mutant Tau induced significant neuronal degeneration in vitro.
- rTau exposure led to a decrease in sodium-dependent Gln uptake in neurons, specifically affecting system A.
- Control ACM reversed rTau-induced neurodegeneration and normalized Gln transport, while rTau-treated astrocytes showed increased Gln uptake via the N system.
Conclusions:
- Alterations in glutamine transport and recycling are key mechanisms in Tau pathology.
- Astrocytes exert neuroprotective effects by modulating the GGC and mitigating Tau-induced neuronal damage.
- Targeting GGC components may offer therapeutic strategies for Tau-related neurodegenerative diseases.
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