SynthesisHuman molecular genetics2011
Cyclin-G-associated kinase modifies α-synuclein expression levels and toxicity in Parkinson's disease: results from the GenePD Study.
Synthesis in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- GWAS-linked GAK locus in Parkinson's disease in Han Chinese and meta-analysis.Human genetics · 2012Pooled it
- Gene expression profiles in Parkinson disease prefrontal cortex implicate FOXO1 and genes under its transcriptional regulation.PLoS genetics · 2012Pooled it
- Shared genetic architecture between DTI-ALPS traits and neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Genetic and environmental risk factors of Parkinsonism.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- GAK antagonises ROCK-dependent regulation of actomyosin dynamics.Journal of cell science · 2026Article
- Clathrin-mediated endocytosis as an axis for the etiopathogenesis of Parkinson's disease.Journal of cell science · 2026Review
- Low-frequency genetic variants in GAK enhance Golgi function and protect against Parkinson's disease.medRxiv : the preprint server for health sciences · 2025Article
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- The Role ofBiomolecules · 2025Review
- α-Synuclein: Multiple pathogenic roles in trafficking and proteostasis pathways in Parkinson's disease.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- Article
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- The cyclin G-associated kinase (GAK) inhibitor SGC-GAK-1 inhibits neurite outgrowth and synapse formation.Molecular brain · 2022Article
- mFrontiers in neurology · 2022Review
- Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics.International journal of molecular medicine · 2021Article
- Association ofFrontiers in genetics · 2021Article
- Cell Cycle Deficits in Neurodegenerative Disorders: Uncovering Molecular Mechanisms to Drive Innovative Therapeutic Development.Aging and disease · 2020Review
- Endosomal sorting pathways in the pathogenesis of Parkinson's disease.Progress in brain research · 2020Review
- SNCA but not DNM3 and GAK modifies age at onset of LRRK2-related Parkinson's disease in Chinese population.Journal of neurology · 2019Article
- Parkinson's disease age at onset genome-wide association study: Defining heritability, genetic loci, and α-synuclein mechanisms.Movement disorders : official journal of the Movement Disorder Society · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Although family history is a well-established risk factor for Parkinson's disease (PD), fewer than 5% of PD cases can be attributed to known genetic mutations. The etiology for the remainder of PD cases is unclear; however, neuronal accumulation of the protein α-synuclein is common to nearly all patients, implicating pathways that influence α-synuclein in PD pathogenesis. We report a genome-wide significant association (P = 3.97 × 10(-8)) between a polymorphism, rs1564282, in the cyclin-G-associated kinase (GAK) gene and increased PD risk, with a meta-analysis odds ratio of 1.48. This association result is based on the meta-analysis of three publicly available PD case-control genome-wide association study and genotyping from a new, independent Italian cohort. Microarray expression analysis of post-mortem frontal cortex from PD and control brains demonstrates a significant association between rs1564282 and higher α-synuclein expression, a known cause of early onset PD. Functional knockdown of GAK in cell culture causes a significant increase in toxicity when α-synuclein is over-expressed. Furthermore, knockdown of GAK in rat primary neurons expressing the A53T mutation of α-synuclein, a well-established model for PD, decreases cell viability. These observations provide evidence that GAK is associated with PD risk and suggest that GAK and α-synuclein interact in a pathway involved in PD pathogenesis. The GAK protein, a serine/threonine kinase, belongs to a family of proteins commonly targeted for drug development. This, combined with GAK's observed relationship to the levels of α-synuclein expression and toxicity, suggests that the protein is an attractive therapeutic target for the treatment of PD.
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Registered trials
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.