ArticleNeurobiology of disease2015
Increased 14-3-3 phosphorylation observed in Parkinson's disease reduces neuroprotective potential of 14-3-3 proteins.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Gene expression meta-analysis of Parkinson's disease and its relationship with Alzheimer's disease.Molecular brain · 2019Pooled it
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Article
- 14-3-3θ phosphorylation at S232 reduces its interactome and regulates axonal trafficking.Disease models & mechanisms · 2025Article
- 14-3-3 Proteins Negatively Regulate Microglial Activation via Inhibition of the NF-κB Pathway.Journal of neurochemistry · 2025Article
- A novel 14-3-3θ phosphomimetic mouse model demonstrates social dominance defects.Biology open · 2025Article
- Rab27b Promotes Lysosomal Function and Alpha-Synuclein Clearance in Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Characterization of multiple binding sites on microtubule associated protein 2c recognized by dimeric and monomeric 14-3-3ζ.The FEBS journal · 2025Article
- 14-3-3θ phosphorylation exacerbates alpha-synuclein aggregation and toxicity.Neurobiology of disease · 2025Article
- 14-3-3 phosphorylation inhibits 14-3-3θ's ability to regulate LRRK2 kinase activity and toxicity.Human molecular genetics · 2024Article
- Protein modification in neurodegenerative diseases.MedComm · 2024Review
- Prospective Role of PAK6 and 14-3-3γ as Biomarkers for Parkinson's Disease.Journal of Parkinson's disease · 2024Article
- Modulating GPCR and 14-3-3 protein interactions: Prospects for CNS drug discovery.Drug discovery today · 2023Review
- LRRK2 and idiopathic Parkinson's disease.Trends in neurosciences · 2022Review
- Mutant glucocerebrosidase impairs α-synuclein degradation by blockade of chaperone-mediated autophagy.Science advances · 2022Article
- Pathways to Parkinson's disease: a spotlight on 14-3-3 proteins.NPJ Parkinson's disease · 2021Review
- 14-3-3 mitigates alpha-synuclein aggregation and toxicity in the in vivo preformed fibril model.Acta neuropathologica communications · 2021Article
- The GTPase Rab27b regulates the release, autophagic clearance, and toxicity of α-synuclein.The Journal of biological chemistry · 2020Article
- Downregulation of 14-3-3 Proteins in Alzheimer's Disease.Molecular neurobiology · 2020Article
- Binding of the Human 14-3-3 Isoforms to Distinct Sites in the Leucine-Rich Repeat Kinase 2.Frontiers in neuroscience · 2020Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
14-3-3 proteins are key regulators of cell survival. We have previously demonstrated that 14-3-3 levels are decreased in an alpha-synuclein (αsyn) mouse model of Parkinson's disease (PD), and that overexpression of certain 14-3-3 isoforms is protective in several PD models. Here we examine whether changes in 14-3-3 phosphorylation may contribute to the neurodegenerative process in PD. We examine three key 14-3-3 phosphorylation sites that normally regulate 14-3-3 function, including serine 58 (S58), serine 184 (S184), and serine/threonine 232 (S/T232), in several models of PD and in human PD brain. We observed that an increase in S232 phosphorylation is observed in rotenone-treated neuroblastoma cells, in cells overexpressing αsyn, and in human PD brains. Alterations in S58 phosphorylation were less consistent in these models, and we did not observe any phosphorylation changes at S184. Phosphorylation at S232 induced by rotenone is reduced by casein kinase inhibitors, and is not dependent on αsyn. Mutation of the S232 site affected 14-3-3θ's neuroprotective effects against rotenone and 1-methyl-4-phenylpyridinium (MPP(+)), with the S232D mutant lacking any protective effect compared to wildtype or S232A 14-3-3θ. The S232D mutant partially reduced the ability of 14-3-3θ to inhibit Bax activation in response to rotenone. Based on these findings, we propose that phosphorylation of 14-3-3s at serine 232 contributes to the neurodegenerative process in PD.
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