4.7 Review

Pathogenic Impact of α-Synuclein Phosphorylation and Its Kinases in α-Synucleinopathies

Related references

Note: Only part of the references are listed.
Article Biochemistry & Molecular Biology

Intermediates of α-synuclein aggregation: Implications in Parkinson's disease pathogenesis

Laxmikant Gadhe et al.

Summary: Although the pathogenic mechanism of synucleinopathies, including Parkinson's disease (PD), is not fully understood, α-synuclein (α-Syn) oligomers may play a significant role in the pathogenesis of PD. These oligomers are neurotoxic and may cause neuronal cell death. However, studying the structure and mechanisms of these oligomers is challenging due to their heterogeneity and transient nature. Understanding the formation and role of α-Syn oligomers can contribute to the development of new therapeutic approaches for PD.

BIOPHYSICAL CHEMISTRY (2022)

Review Pharmacology & Pharmacy

Impact of fatty acid-binding proteins and dopamine receptors on α-synucleinopathy

Ichiro Kawahata et al.

Summary: An aging society leads to an increased number of patients with cognitive and movement disorders. This review focuses on the role of FABP3, dopamine receptors, and other FABP family proteins in the process of alpha-synuclein propagation and the subsequent aggregate-induced cytotoxicity, and proposes the potential of FABP as a therapeutic target for alpha-synucleinopathies.

JOURNAL OF PHARMACOLOGICAL SCIENCES (2022)

Article Neurosciences

The Compound ATH434 Prevents Alpha-Synuclein Toxicity in a Murine Model of Multiple System Atrophy

David Finkelstein et al.

Summary: This study demonstrates that ATH434 has potential efficacy in a mouse model of MSA, reducing alpha-synuclein aggregation, decreasing pathology, and preserving neurons.

JOURNAL OF PARKINSONS DISEASE (2022)

Article Biochemistry & Molecular Biology

Genetic deletion of Polo-like kinase 2 reduces alpha-synuclein serine-129 phosphorylation in presynaptic terminals but not Lewy bodies

Leah J. Weston et al.

Summary: PLK2 is a potential Lewy body kinase, and its deletion reduces the phosphorylation level of α-synuclein at presynaptic terminals but has no effect on phosphorylation levels in Lewy bodies. Inhibition of PLK2 shows promise in developing new therapeutics, yet the mechanism of neuroprotection through PLK2 inhibition is unlikely due to reducing α-synuclein phosphorylation. The true Lewy body kinase still awaits discovery.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

Article Biochemistry & Molecular Biology

Dopamine D2 Long Receptors Are Critical for Caveolae-Mediated α-Synuclein Uptake in Cultured Dopaminergic Neurons

Ichiro Kawahata et al.

Summary: The study showed that dopamine D-2L receptors combined with FABP3 play a critical role in the uptake of alpha-synuclein by dopaminergic neurons. This finding suggests a novel pathogenic mechanism for synucleinopathies, including Parkinson's disease.

BIOMEDICINES (2021)

Article Multidisciplinary Sciences

Polo-like kinase 2 inhibition reduces serine-129 phosphorylation of physiological nuclear alpha-synuclein but not of the aggregated alpha-synuclein

Sara Elfarrash et al.

Summary: The study investigated the impact of PLK2 inhibition on alpha-synuclein phosphorylation, revealing that PLK2 inhibition reduces the nuclear soluble pS129 level. The findings suggest that PLK2 is likely involved in the S129 phosphorylation of the soluble physiological fraction of alpha-synuclein.

PLOS ONE (2021)

Article Neurosciences

Tyrosine 136 phosphorylation of α-synuclein aggregates in the Lewy body dementia brain: involvement of serine 129 phosphorylation by casein kinase 2

Kazunori Sano et al.

Summary: The phosphorylation of alpha synuclein at Y136 in the Lewy body dementia brain is mediated by the unexpected kinase activity of CK2. CK2 can promote aggregate formation of r-alpha Syn with phosphorylation at S129 and Y136, while its inhibition attenuates the formation of aggregates with S129 phosphorylation and unexpectedly increases phosphorylation at Y136.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2021)

Article Neurosciences

In vivo aggregation of presynaptic alpha-synuclein is not influenced by its phosphorylation at serine-129

Leah J. Weston et al.

Summary: Abnormal aggregation of α-synuclein is a key feature of neurodegenerative diseases, but the mechanisms behind this aggregation remain unclear. Using a zebrafish model, researchers were able to express and measure various forms of human α-synuclein and found distinct pools of the protein with different mobility, indicating different subpopulations of aggregated and non-aggregated protein. Phosphorylation at serine-129 does not significantly affect the mobility of α-synuclein, suggesting that it alone does not promote protein aggregation.

NEUROBIOLOGY OF DISEASE (2021)

Article Biochemistry & Molecular Biology

T-Type Ca2+ Enhancer SAK3 Activates CaMKII and Proteasome Activities in Lewy Body Dementia Mice Model

Jing Xu et al.

Summary: SAK3 activates CaMKII to enhance proteasomal activity, leading to the degradation of α-Syn and slowing down the progression of LBD. This study reveals the promoting effect of SAK3 on α-Syn pathology.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Biochemistry & Molecular Biology

An α-synuclein decoy peptide prevents cytotoxic α-synuclein aggregation caused by fatty acid binding protein 3

Naoya Fukui et al.

Summary: The study found that the binding of FABP3 protein to αSyn protein alters the aggregation mechanism of αSyn, enhancing its cytotoxicity towards cells, and can be disrupted by αSynP130-140. This discovery may help prevent the accumulation of toxic FABP3-αSyn oligomers in cells, thereby halting the progression of Parkinson's disease.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

Article Clinical Neurology

Plasma and Serum Alpha-Synuclein as a Biomarker of Diagnosis in Patients With Parkinson's Disease

Chun-Wei Chang et al.

FRONTIERS IN NEUROLOGY (2020)

Review Biochemistry & Molecular Biology

Degradation of Tyrosine Hydroxylase by the Ubiquitin-Proteasome System in the Pathogenesis of Parkinson's Disease and Dopa-Responsive Dystonia

Ichiro Kawahata et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

Article Clinical Neurology

Plasma alpha-synuclein detected by single molecule array is increased in PD

Adeline S. L. Ng et al.

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY (2019)

Article Neurosciences

Pathogenic alpha-synuclein aggregates preferentially bind to mitochondria and affect cellular respiration

Xinhe Wang et al.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2019)

Review Neurosciences

Brain-First versus Gut-First Parkinson's Disease: A Hypothesis

Per Borghammer et al.

JOURNAL OF PARKINSONS DISEASE (2019)

Article Biochemistry & Molecular Biology

Fatty Acid-Binding Protein 3 is Critical for α-Synuclein Uptake and MPP+-Induced Mitochondrial Dysfunction in Cultured Dopaminergic Neurons

Ichiro Kawahata et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

Article Clinical Neurology

Gut-brain axis and the spread of α-synuclein pathology: Vagal highway or dead end?

David P. Breen et al.

MOVEMENT DISORDERS (2019)

Article Neurosciences

Extracellular α-synuclein levels are regulated by neuronal activity

Kaoru Yamada et al.

MOLECULAR NEURODEGENERATION (2018)

Review Neurosciences

Import and Export of Misfoldeda alpha-Synuclein

Lilia Rodriguez et al.

FRONTIERS IN NEUROSCIENCE (2018)

Article Chemistry, Multidisciplinary

Alpha-Synuclein Modulates the Physical Properties of DNA

Kai Jiang et al.

CHEMISTRY-A EUROPEAN JOURNAL (2018)

Article Cell Biology

α-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson's disease

Roberto Di Maio et al.

SCIENCE TRANSLATIONAL MEDICINE (2016)

Article Multidisciplinary Sciences

α-Synuclein enhances histone H3 lysine-9 dimethylation and H3K9me2-dependent transcriptional responses

Naoto Sugeno et al.

SCIENTIFIC REPORTS (2016)

Article Multidisciplinary Sciences

A small-angle X-ray scattering study of alpha-synuclein from human red blood cells

Katsuya Araki et al.

SCIENTIFIC REPORTS (2016)

Article Biochemistry & Molecular Biology

Dopamine or biopterin deficiency potentiates phosphorylation at 40Ser and ubiquitination of tyrosine hydroxylase to be degraded by the ubiquitin proteasome system

Ichiro Kawahata et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2015)

Article Biochemistry & Molecular Biology

α-Synuclein interactions with phospholipid model membranes: Key roles for electrostatic interactions and lipid-bilayer structure

Katja Pirc et al.

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES (2015)

Article Biochemistry & Molecular Biology

α-synuclein assemblies sequester neuronal α3-Na+/K+-ATPase and impair Na+ gradient

Amulya Nidhi Shrivastava et al.

EMBO JOURNAL (2015)

Article Medicine, General & Internal

Parkinson's disease

Lorraine V. Kalia et al.

LANCET (2015)

Article Clinical Neurology

Cutaneous neuropathy in Parkinson's disease: a window into brain pathology

Kathrin Doppler et al.

ACTA NEUROPATHOLOGICA (2014)

Article Biochemistry & Molecular Biology

Polo-like kinase 2 activates an antioxidant pathway to promote the survival of cells with mitochondrial dysfunction

Jie Li et al.

FREE RADICAL BIOLOGY AND MEDICINE (2014)

Article Biochemistry & Molecular Biology

In Vitro Phosphorylation Does not Influence the Aggregation Kinetics of WT α-Synuclein in Contrast to Its Phosphorylation Mutants

Sarah Schreurs et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2014)

Article Clinical Neurology

Skin nerve α-synuclein deposits A biomarker for idiopathic Parkinson disease

Vincenzo Donadio et al.

NEUROLOGY (2014)

Article Multidisciplinary Sciences

Modelling Ser129 Phosphorylation Inhibits Membrane Binding of Pore-Forming Alpha-Synuclein Oligomers

Georg Sebastian Nuebling et al.

PLOS ONE (2014)

Review Neurosciences

Protein phosphorylation in neurodegeneration: friend or foe?

Sandra Tenreiro et al.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2014)

Article Chemistry, Medicinal

Design and synthesis of highly selective, orally active Polo-like kinase-2 (Plk-2) inhibitors

Simeon Bowers et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2013)

Article Clinical Neurology

Prion-like spreading of pathological α-synuclein in brain

Masami Masuda-Suzukake et al.

BRAIN (2013)

Article Genetics & Heredity

LRRK2 interactions with α-synuclein in Parkinson's disease brains and in cell models

Patricia Silva Guerreiro et al.

JOURNAL OF MOLECULAR MEDICINE-JMM (2013)

Article Biochemistry & Molecular Biology

Pramipexole Reduces Phosphorylation of α-Synuclein at Serine-129

Kai-Yin Chau et al.

JOURNAL OF MOLECULAR NEUROSCIENCE (2013)

Article Multidisciplinary Sciences

Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia

Changyoun Kim et al.

NATURE COMMUNICATIONS (2013)

Article Multidisciplinary Sciences

A longitudinal study on α-synuclein in blood plasma as a biomarker for Parkinson's disease

Penelope G. Foulds et al.

SCIENTIFIC REPORTS (2013)

Article Clinical Neurology

Lewy pathology in gastric and duodenal biopsies in Parkinson's Disease

Helene Pouclet et al.

MOVEMENT DISORDERS (2012)

Article Cell Biology

From Plk1 to Plk5 Functional evolution of Polo-like kinases

Guillermo de Carcer et al.

CELL CYCLE (2011)

Article Clinical Neurology

Transmission of Prion Strains in a Transgenic Mouse Model Overexpressing Human A53T Mutated α-Synuclein

Anne-Laure J. Mougenot et al.

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY (2011)

Article Neurosciences

Characterization of Kinases Involved in the Phosphorylation of Aggregated α-Synuclein

Elisa A. Waxman et al.

JOURNAL OF NEUROSCIENCE RESEARCH (2011)

Article Multidisciplinary Sciences

The AAA-ATPase VPS4 Regulates Extracellular Secretion and Lysosomal Targeting of α-Synuclein

Takafumi Hasegawa et al.

PLOS ONE (2011)

Article Biochemistry & Molecular Biology

Phosphorylation of Synucleins by Members of the Polo-like Kinase Family

Martial K. Mbefo et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2010)

Article Clinical Neurology

Plasma α-Synuclein in Patients with Parkinson's Disease With and Without Treatment

Raquel Duran et al.

MOVEMENT DISORDERS (2010)

Article Biochemistry & Molecular Biology

Lrrk2 interaction with α-synuclein in diffuse Lewy body disease

Hong Qing et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2009)

Article Biochemistry & Molecular Biology

Lrrk2 phosphorylates alpha synuclein at serine 129: Parkinson disease implications

Hong Qing et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2009)

Review Biochemistry & Molecular Biology

Phosphorylation does not prompt, nor prevent, the formation of alpha-synuclein toxic species in a rat model of Parkinson's disease

Samareh Azeredo da Silveira et al.

HUMAN MOLECULAR GENETICS (2009)

Article Biochemistry & Molecular Biology

Polo-like Kinase 2 (PLK2) Phosphorylates α-Synuclein at Serine 129 in Central Nervous System

Kelly J. Inglis et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2009)

Article Biochemistry & Molecular Biology

α-Synuclein Aggregation and Ser-129 Phosphorylation-dependent Cell Death in Oligodendroglial Cells

Christine L. Kragh et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2009)

Review Clinical Neurology

Biological fluid biomarkers in neurodegenerative parkinsonism

Michael Eller et al.

NATURE REVIEWS NEUROLOGY (2009)

Article Biochemistry & Molecular Biology

Modulation of α-Synuclein Aggregation by Dopamine: A Review

Su Ling Leong et al.

NEUROCHEMICAL RESEARCH (2009)

Article Multidisciplinary Sciences

Exogenous α-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells

Kelvin C. Luk et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2009)

Article Biochemistry & Molecular Biology

Phosphorylation at Ser-129 but not the phosphomimics S129E/D inhibits the fibrillation of α-synuclein

Katerina E. Paleologou et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2008)

Article Clinical Neurology

Localization of CKII β subunits in Lewy bodies of Parkinson's disease

Myung Yi Ryu et al.

JOURNAL OF THE NEUROLOGICAL SCIENCES (2008)

Article Biochemistry & Molecular Biology

Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease

Jeffrey H. Kordower et al.

NATURE MEDICINE (2008)

Article Multidisciplinary Sciences

The phosphorylation state of Ser-129 in human α-synuclein determines neurodegeneration in a rat model of Parkinson disease

Oleg S. Gorbatyuk et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

Review Biochemistry & Molecular Biology

Interactions between metals and α-synuclein -: function or artefact?

David R. Brown

FEBS JOURNAL (2007)

Article Neurosciences

Plasma α-synuclein is decreased in subjects with Parkinson's disease

Qiao-Xin Li et al.

EXPERIMENTAL NEUROLOGY (2007)

Article Geriatrics & Gerontology

Age-dependent cognitive decline and amygdala pathology in alpha-synuclein transgenic mice

Christian Freichel et al.

NEUROBIOLOGY OF AGING (2007)

Article Biochemistry & Molecular Biology

Decreased α-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease

Takahiko Tokuda et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2006)

Article Neurosciences

The role of G-protein-coupled receptor kinase 5 in pathogenesis of sporadic Parkinson's disease

Shigeki Arawaka et al.

JOURNAL OF NEUROSCIENCE (2006)

Article Multidisciplinary Sciences

Structure and properties of α-synuclein and other amyloids determined at the amino acid level

C Del Mar et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2005)

Article Clinical Neurology

An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family

M Funayama et al.

ANNALS OF NEUROLOGY (2005)

Article Biochemistry & Molecular Biology

Nuclear localization of α-synuclein and its interaction with histones

J Goers et al.

BIOCHEMISTRY (2003)

Article Multidisciplinary Sciences

Initiation and synergistic fibrillization of tau and alpha-synuclein

BI Giasson et al.

SCIENCE (2003)

Review Geriatrics & Gerontology

Staging of brain pathology related to sporadic Parkinson's disease

H Braak et al.

NEUROBIOLOGY OF AGING (2003)

Article Biochemistry & Molecular Biology

Phosphorylated α-synuclein is ubiquitinated in α-synucleinopathy lesions

M Hasegawa et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2002)

Article Biochemistry & Molecular Biology

Hyperphosphorylation and insolubility of α-synuclein in transgenic mouse oligodendrocytes

PJ Kahle et al.

EMBO REPORTS (2002)

Article Neurosciences

A role for α-synuclein in the regulation of dopamine biosynthesis

RG Perez et al.

JOURNAL OF NEUROSCIENCE (2002)

Article Cell Biology

α-Synuclein is phosphorylated in synucleinopathy lesions

H Fujiwara et al.

NATURE CELL BIOLOGY (2002)

Review Neurosciences

Alpha-synuclein and neurodegenerative diseases

M Goedert

NATURE REVIEWS NEUROSCIENCE (2001)

Article Biochemistry & Molecular Biology

Conformational properties of α-synuclein in its free and lipid-associated states

D Eliezer et al.

JOURNAL OF MOLECULAR BIOLOGY (2001)

Article Biochemistry & Molecular Biology

Synucleins are a novel class of substrates for G protein-coupled receptor kinases

AN Pronin et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2000)

Article Biochemistry & Molecular Biology

Constitutive phosphorylation of the Parkinson's disease associated α-synuclein

M Okochi et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2000)