ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2009
Alpha-Synuclein contributes to GSK-3beta-catalyzed Tau phosphorylation in Parkinson's disease models.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
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Who cites it
155 citing papers in PubMed, 263 citations in OpenAlex.
- Andrographolide: Mechanisms and Therapeutic Potential in Alzheimer's and Parkinson's Disease.Molecules (Basel, Switzerland) · 2026Review
- When Pathologies Collide: The Intersection of Tau and Alpha-Synuclein in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Tau physiology and pathology: impacts on cellular structures and neurodegenerative diseases.Inflammopharmacology · 2026Review
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- IgLON5 autoimmune antibodies activate Tau via neuronal hyperactivity.Science advances · 2026Article
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Narrative Review "Dual Frontiers in Neurodegeneration: Pharmacological Synergies and Divergences in Parkinson's Disease and Type 2 Diabetes Mellitus".Cellular and molecular neurobiology · 2026Review
- Discovery of multitargeting single agents as a novel route to the potential treatment of neurodegenerative diseases.Bioorganic & medicinal chemistry letters · 2026Article
- Tau protein in Parkinson's disease: advances in phosphoproteomics and molecular dynamics simulations.Frontiers in aging neuroscience · 2026Review
- Lithium as a disease-modifying therapy for Parkinson's disease: mechanisms, preclinical evidence, and clinical prospects.Clinical parkinsonism & related disorders · 2026Review
- Tau protein: Physiological functions and multifaceted roles in neurodegenerative and psychiatric disorders.Genomic psychiatry : advancing science from genes to society · 2025Article
- Human Wild-Type α-Synuclein Drives Progressive Tau Pathology in a Disease-Relevant Mouse Model of Synucleinopathy.Research square · 2025Article
- Co-Expression of Mutant Tau and α-Synuclein in Neurons Promotes Tau Phosphorylation, Neuronal Loss, and Neuroinflammation in Mouse Brain.Molecular neurobiology · 2025Article
- Converging pathologies in neurodegeneration: the mechanistic interplay between α-Synuclein and Tau in Alzheimer's and Parkinson's.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Article
- Lewy body dementia: exploring biomarkers and pathogenic interactions of amyloid β, tau, and α-synuclein.Molecular neurodegeneration · 2025Review
- Article
- Integrative machine learning and molecular simulation approaches identify GSK3β inhibitors for neurodegenerative disease therapy.Scientific reports · 2025Article
- The Comorbidity of AD and PD: Exploring Clinical, Pathological, and Biomarker Interactions.Aging and disease · 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
95 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
We have shown in the parkinsonism-inducing neurotoxin MPP(+)/MPTP model that alpha-Synuclein (alpha-Syn), a presynaptic protein causal in Parkinson's disease (PD), contributes to hyperphosphorylation of Tau (p-Tau), a protein normally linked to tauopathies, such as Alzheimer's disease (AD). Here, we investigated the kinase involved and show that the Tau-specific kinase, glycogen synthase kinase 3beta (GSK-3beta), is robustly activated in various MPP(+)/MPTP models of Parkinsonism (SH-SY5Y cotransfected cells, mesencephalic neurons, transgenic mice overexpressing alpha-Syn, and postmortem striatum of PD patients). The activation of GSK-3beta was absolutely dependent on the presence of alpha-Syn, as indexed by the absence of p-GSK-3beta in cells lacking alpha-Syn and in alpha-Syn KO mice. MPP(+) treatment induced translocation and accumulation of p-GSK-3beta in nuclei of SH-SY5Y cells and mesencephalic neurons. Through coimmunoprecipitation (co-IP), we found that alpha-Syn, pSer396/404-Tau, and p-GSK-3beta exist as a heterotrimeric complex in SH-SY5Y cells. GSK-3beta inhibitors (lithium and TDZD-8) protected against MPP(+)-induced events in SH-SY5Y cells, preventing cell death and p-GSK-3beta formation, by reversing increases in alpha-Syn accumulation and p-Tau formation. These data unveil a previously unappreciated role of alpha-Syn in the induction of p-GSK-3beta, and demonstrate the importance of this kinase in the genesis and maintenance of neurodegenerative changes associated with PD.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.