ArticleThe Journal of biological chemistry2010
Serine 129 phosphorylation reduces the ability of alpha-synuclein to regulate tyrosine hydroxylase and protein phosphatase 2A in vitro and in vivo.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 109 citations in OpenAlex.
- Mechanisms of Brain Aging and Their Links to Alzheimer's and Parkinson's Disease Pathology.International journal of molecular sciences · 2026Review
- Protein phosphatase 2A methylation state impacts α-synucleinopathy in mouse models.Cell death discovery · 2026Article
- Pathogenic mechanism underlying parkinsonism induced by neurotoxicants (MPTP and 6-hydroxydopamine) and α-synuclein: a unifying hypothesis.Journal of molecular cell biology · 2025Review
- GDNF attenuates a-synuclein aggregation-induced damage to VTA-NAc dopaminergic transmission and alleviates depression-like behaviors in mice.Scientific reports · 2025Article
- Disease-specific neuropathological alterations of the locus coeruleus in Alzheimer's disease, Down syndrome, and Parkinson's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Clavulanic acid inhibits methamphetamine locomotor sensitization in mice and normalizes methamphetamine-induced changes in glutaminase mRNA levels in the nucleus accumbens.Physiology & behavior · 2024Article
- PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability.Brain : a journal of neurology · 2023Article
- Article
- Pathogenic Impact of α-Synuclein Phosphorylation and Its Kinases in α-Synucleinopathies.International journal of molecular sciences · 2022Review
- A Matrigel-based 3D construct of SH-SY5Y cells models the α-synuclein pathologies of Parkinson's disease.Disease models & mechanisms · 2022Article
- Polo-Like Kinase 2: From Principle to Practice.Frontiers in oncology · 2022Review
- Trophoblast glycoprotein is a new candidate gene for Parkinson's disease.NPJ Parkinson's disease · 2021Article
- Enhanced tyrosine hydroxylase activity induces oxidative stress, causes accumulation of autotoxic catecholamine metabolites, and augments amphetamine effects in vivo.Journal of neurochemistry · 2021Article
- Intranasal Carnosine Mitigates α-Synuclein Pathology and Motor Dysfunction in the Thy1-aSyn Mouse Model of Parkinson's Disease.ACS chemical neuroscience · 2021Article
- Neurons and Glia Interplay in α-Synucleinopathies.International journal of molecular sciences · 2021Review
- The Role of Cholesterol in α-Synuclein and Lewy Body Pathology in GBA1 Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2021Review
- Molecular crosstalk between cancer and neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2020Review
- Degradation of Tyrosine Hydroxylase by the Ubiquitin-Proteasome System in the Pathogenesis of Parkinson's Disease and Dopa-Responsive Dystonia.International journal of molecular sciences · 2020Review
- Targeting α-synuclein for PD Therapeutics: A Pursuit on All Fronts.Biomolecules · 2020Review
- FTY720-Mitoxy reduces synucleinopathy and neuroinflammation, restores behavior and mitochondria function, and increases GDNF expression in Multiple System Atrophy mouse models.Experimental neurology · 2020Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Alpha-synuclein (a-Syn), a protein implicated in Parkinson disease, contributes significantly to dopamine metabolism. a-Syn binding inhibits the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis. Phosphorylation of TH stimulates its activity, an effect that is reversed by protein phosphatase 2A (PP2A). In cells, a-Syn overexpression activates PP2A. Here we demonstrate that a-Syn significantly inhibited TH activity in vitro and in vivo and that phosphorylation of a-Syn serine 129 (Ser-129) modulated this effect. In MN9D cells, a-Syn overexpression reduced TH serine 19 phosphorylation (Ser(P)-19). In dopaminergic tissues from mice overexpressing human a-Syn in catecholamine neurons only, TH-Ser-19 and TH-Ser-40 phosphorylation and activity were also reduced, whereas PP2A was more active. Cerebellum, which lacks excess a-Syn, had PP2A activity identical to controls. Conversely, a-Syn knock-out mice had elevated TH-Ser-19 phosphorylation and activity and less active PP2A in dopaminergic tissues. Using an a-Syn Ser-129 dephosphorylation mimic, with serine mutated to alanine, TH was more inhibited, whereas PP2A was more active in vitro and in vivo. Phosphorylation of a-Syn Ser-129 by Polo-like-kinase 2 in vitro reduced the ability of a-Syn to inhibit TH or activate PP2A, identifying a novel regulatory role for Ser-129 on a-Syn. These findings extend our understanding of normal a-Syn biology and have implications for the dopamine dysfunction of Parkinson disease.
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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.