ArticleProceedings of the National Academy of Sciences of the United States of America2013
Polo-like kinase 2 regulates selective autophagic α-synuclein clearance and suppresses its toxicity in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed, 209 citations in OpenAlex.
- Brain insulin resistance as a driver of proteinopathy in neurodegeneration: from cell-type-specific mechanisms to targeted therapeutics.Translational neurodegeneration · 2026Review
- From synaptic development to degeneration: a narrative review of small molecule strategies targeting alpha-synuclein in Parkinson's disease.Metabolic brain disease · 2026Review
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Long-term isolation and archaic introgression shape functional genetic variation in Near Oceania.Science (New York, N.Y.) · 2026Article
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Imaging spatial transcriptomics reveals molecular patterns underlying accumulation of p-Ser129 α-synuclein in a transgenic mouse model.NPJ Parkinson's disease · 2026Article
- Research progress on the α-synuclein-lysosome axis in Parkinson's disease: molecular mechanisms of protein aggregation, autophagy dysfunction, and therapeutic targeting.Frontiers in neuroscience · 2026Review
- Identification and histological validation of autophagy-related core genes ADRB2 and PLK2 in keloids, with integrated immune infiltration analysis.Frontiers in immunology · 2026Article
- Alpha-Synuclein Neurobiology in Parkinson's Disease: A Comprehensive Review of Its Role, Mechanisms, and Therapeutic Perspectives.Brain sciences · 2025Review
- Article
- Age-dependent progression from clearance to vulnerability in the early response of periventricular microglia to α-synuclein toxic species.Molecular neurodegeneration · 2025Article
- Darling (v2.0): Mining disease-related databases for the detection of biomedical entity associations.Computational and structural biotechnology journal · 2025Article
- Article
- Posttranslational Modifications ofPharmacological reviews · 2024Review
- PLK2-mediated phosphorylation of SQSTM1 S349 promotes aggregation of polyubiquitinated proteins upon proteasomal dysfunction.Autophagy · 2024Article
- The role of polo-like kinases 2 in the proteasomal and lysosomal degradation of alpha-synuclein in neurons.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Neuroprotection of low dose carbon monoxide in Parkinson's disease models commensurate with the reduced risk of Parkinson's among smokers.NPJ Parkinson's disease · 2024Article
- RXR nuclear receptor signaling modulates lipid metabolism and triggers lysosomal clearance of alpha-synuclein in neuronal models of synucleinopathy.Cellular and molecular life sciences : CMLS · 2024Article
- Physiological roles of α-synuclein serine-129 phosphorylation - not an oxymoron.Trends in neurosciences · 2024Review
- An antioxidant and anti-ER stress combination therapy elevates phosphorylation of α-Syn at serine 129 and alleviates post-TBI PD-like pathology in a sex-specific manner in mice.Experimental neurology · 2024Article
62 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An increase in α-synuclein levels due to gene duplications/triplications or impaired degradation is sufficient to trigger its aggregation and cause familial Parkinson disease (PD). Therefore, lowering α-synuclein levels represents a viable therapeutic strategy for the treatment of PD and related synucleinopathies. Here, we report that Polo-like kinase 2 (PLK2), an enzyme up-regulated in synucleinopathy-diseased brains, interacts with, phosphorylates and enhances α-synuclein autophagic degradation in a kinase activity-dependent manner. PLK2-mediated degradation of α-synuclein requires both phosphorylation at S129 and PLK2/α-synuclein complex formation. In a rat genetic model of PD, PLK2 overexpression reduces intraneuronal human α-synuclein accumulation, suppresses dopaminergic neurodegeneration, and reverses hemiparkinsonian motor impairments induced by α-synuclein overexpression. This PLK2-mediated neuroprotective effect is also dependent on PLK2 activity and α-synuclein phosphorylation. Collectively, our findings demonstrate that PLK2 is a previously undescribed regulator of α-synuclein turnover and that modulating its kinase activity could be a viable target for the treatment of synucleinopathies.
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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.