ArticleThe Journal of biological chemistry
Genetic deletion of Polo-like kinase 2 reduces alpha-synuclein serine-129 phosphorylation in presynaptic terminals but not Lewy bodies.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Imaging spatial transcriptomics reveals molecular patterns underlying accumulation of p-Ser129 α-synuclein in a transgenic mouse model.NPJ Parkinson's disease · 2026Article
- Article
- Uncovering Cell Cycle Dysregulations and Associated Mechanisms in Cancer and Neurodegenerative Disorders: A Glimpse of Hope for Repurposed Drugs.Molecular neurobiology · 2024Review
- Article
- Posttranslational Modifications ofPharmacological reviews · 2024Review
- PLK2-mediated phosphorylation of SQSTM1 S349 promotes aggregation of polyubiquitinated proteins upon proteasomal dysfunction.Autophagy · 2024Article
- Evaluation of the Effect of β-Wrapin AS69 in a Mouse Model Based on Alpha-Synuclein Overexpression.Biomolecules · 2024Article
- Excess phosphoserine-129 α-synuclein induces synaptic vesicle trafficking and declustering defects at a vertebrate synapse.Molecular biology of the cell · 2024Article
- Polo-like kinase inhibition leads to neuroprotection of neurons bearing alpha-synuclein Lewy body-like inclusionsmicroPublication biology · 2024Article
- Article
- Unraveling the Complex Interplay between Alpha-Synuclein and Epigenetic Modification.International journal of molecular sciences · 2023Review
- Dynamic physiological α-synuclein S129 phosphorylation is driven by neuronal activity.NPJ Parkinson's disease · 2023Article
- Conserved gene signatures shared amongFrontiers in molecular biosciences · 2023Article
- Aggregated Alpha-Synuclein Inclusions within the Nucleus Predict Impending Neuronal Cell Death in a Mouse Model of Parkinsonism.International journal of molecular sciences · 2022Article
- Pathogenic Impact of α-Synuclein Phosphorylation and Its Kinases in α-Synucleinopathies.International journal of molecular sciences · 2022Review
- Dopamine Transporter, PhosphoSerine129 α-Synuclein and α-Synuclein Levels in Aged LRRK2 G2019S Knock-In and Knock-Out Mice.Biomedicines · 2022Article
- Miro proteins and their role in mitochondrial transfer in cancer and beyond.Frontiers in cell and developmental biology · 2022Review
- Polo-Like Kinase 2: From Principle to Practice.Frontiers in oncology · 2022Review
- Alpha-Synuclein and Cognitive Decline in Parkinson Disease.Life (Basel, Switzerland) · 2021Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Phosphorylation of alpha-synuclein at serine-129 is an important marker of pathologically relevant, aggregated forms of the protein in several important human diseases, including Parkinson's disease, Dementia with Lewy bodies, and Multiple system atrophy. Although several kinases have been shown to be capable of phosphorylating alpha-synuclein in various model systems, the identity of the kinase that phosphorylates alpha-synuclein in the Lewy body remains unknown. One member of the Polo-like kinase family, PLK2, is a strong candidate for being the Lewy body kinase. To examine this possibility, we have used a combination of approaches, including biochemical, immunohistochemical, and in vivo multiphoton imaging techniques to study the consequences of PLK2 genetic deletion on alpha-synuclein phosphorylation in both the presynaptic terminal and preformed fibril-induced Lewy body pathology in mouse cortex. We find that PLK2 deletion reduces presynaptic terminal alpha-synuclein serine-129 phosphorylation, but has no effect on Lewy body phosphorylation levels. Serine-129 mutation to the phosphomimetic alanine or the unphosphorylatable analog aspartate does not change the rate of cell death of Lewy inclusion-bearing neurons in our in vivo multiphoton imaging paradigm, but PLK2 deletion does slow the rate of neuronal death. Our data indicate that inhibition of PLK2 represents a promising avenue for developing new therapeutics, but that the mechanism of neuroprotection by PLK2 inhibition is not likely due to reducing alpha-synuclein serine-129 phosphorylation and that the true Lewy body kinase still awaits discovery.
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