ArticleActa neuropathologica communications2020
Phosphorylation and oligomerization of α-synuclein associated with GSK-3β activation in the rTg4510 mouse model of tauopathy.
Article in Acta neuropathologica communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 20 citations in OpenAlex.
- Targeting protein aggregate co-pathologies in neurodegeneration: a viable therapeutic strategy?Molecular neurodegeneration advances · 2026Review
- Lewy body dementia: exploring biomarkers and pathogenic interactions of amyloid β, tau, and α-synuclein.Molecular neurodegeneration · 2025Review
- Development of Positron Emission Tomography Radiotracers for Imaging α-Synuclein Aggregates.Cells · 2025Review
- Unravelling the Proteinopathic Engagement of α-Synuclein, Tau, and Amyloid Beta in Parkinson's Disease: Mitochondrial Collapse as a Pivotal Driver of Neurodegeneration.Neurochemical research · 2025Review
- Serine-129 phosphorylatedFrontiers in aging neuroscience · 2025Article
- Posttranslational Modifications ofPharmacological reviews · 2024Review
- Mutant mice with rod-specific VPS35 deletion exhibit retinal α-synuclein pathology-associated degeneration.Nature communications · 2024Article
- Synthesis and preliminary evaluation of novel PET probes for GSK-3 imaging.Scientific reports · 2024Article
- Occurrence of Total and Proteinase K-Resistant Alpha-Synuclein in Glioblastoma Cells Depends on mTOR Activity.Cancers · 2022Article
- Parkinson's Disease Dementia: Synergistic Effects of Alpha-Synuclein, Tau, Beta-Amyloid, and Iron.Frontiers in aging neuroscience · 2021Article
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7 authors at 3 institutions in 1 country.
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Abstract
Neurodegenerative diseases are characterized by the accumulation of specific phosphorylated protein aggregates in the brain, such as hyperphosphorylated tau (hp-tau) in tauopathies and phosphorylated α-synuclein (p-αSyn) in α-synucleinopathies. The simultaneous accumulation of different proteins is a common event in many neurodegenerative diseases. We herein describe the detection of the phosphorylation and dimerization of αSyn and activation of GSK-3β, a major kinase known to phosphorylate tau and αSyn, in the brains of rTg4510 mice that overexpress human P301L mutant tau. Immunohistochemistry showed p-αSyn aggregates in rTg4510 mice, which were suppressed by doxycycline-mediated decreases in mutant tau expression levels. A semi-quantitative analysis revealed a regional correlation between hp-tau and p-αSyn accumulation in rTg4510 mice. Furthermore, proteinase K-resistant αSyn aggregates were found in the region with excessive hp-tau accumulation in rTg4510 mice, and these aggregates were morphologically different from proteinase K-susceptible p-αSyn aggregates. Western blotting revealed decreases in p-αSyn monomers in TBS- and sarkosyl-soluble fractions and increases in ubiquitinated p-αSyn dimers in sarkosyl-soluble and insoluble fractions in rTg4510 mice. Furthermore, an activated form of GSK-3β was immunohistochemically detected within cells containing both hp-tau and p-αSyn aggregates. A semi-quantitative analysis revealed that increased GSK-3β activity strongly correlated with hp-tau and p-αSyn accumulation in rTg4510 mice. Collectively, the present results suggest that the overexpression of human P301L mutant tau promoted the phosphorylation and dimerization of endogenous αSyn by activating GSK-3β in rTg4510 mice. This synergic effect between tau, αSyn, and GSK-3β may be involved in the pathophysiology of several neurodegenerative diseases that show the accumulation of both tau and αSyn.
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