|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
E46K mutant α-synuclein is more degradation resistant and exhibits greater toxic effects than wild-type α-synuclein in Drosophila models of Parkinson's disease.
|
31242217 |
2019 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Three missense mutations (A30P, A53T and E46K) in the alpha-syn gene are associated with rare autosomal dominant forms of familial PD.
|
18808659 |
2008 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.
|
23505409 |
2013 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
The cytotoxicity was significantly lower in SH-SY5Y-γ-syn cells, while transient overexpression of wt α-syn or its PD mutants (A30P and E46K, but not A53T) modestly (but still significantly) rescued the cytotoxicity of PA in SH-SY5Y and T98G cells.
|
29713567 |
2018 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
We investigated alpha-synuclein mutations, causative for autosomal dominant forms of Parkinson's disease (A30P, A53T and E46K), and phosphorylation mutants at serine 129 (S129A and S129D) using fluorescently labelled alpha-synuclein, actin and tau.
|
17408955 |
2007 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Among familial forms of PD, a small fraction is caused by missense (A53T, A30P and E46K) and copy number mutations in SNCA which encodes alpha-synuclein, a primary protein constituent of Lewy bodies, the pathognomonic protein aggregates found in neurons in PD.
|
20106867 |
2010 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Genetic studies have revealed that rare point mutations in the gene encoding α-synuclein including A30P, A53T, and E46K are associated with familial forms of PD, indicating a pathological role for mutant α-synuclein in PD etiology.
|
24833599 |
2014 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
In this study, we created a BAC (bacterial artificial chromosome) transgenic rat model of PD expressing the E46K mutation of α-synuclein, which is pathogenic in humans.
|
23153578 |
2013 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Such E46K-like mutants have been shown to cause dopaminergic neuron loss and severe but L-DOPA-responsive motor defects in mouse overexpression models, presenting enormous translational potential for PD and other "synucleinopathies."
|
31048377 |
2019 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
In summary, we successfully generated Guangxi Bama minipigs harboring three PD-casusing mutations (E46K, H50Q and G51D) in SCNA.
|
30127453 |
2018 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Here, we generated mice expressing the fPD E46K mutation plus 2 homologous E→K mutations in adjacent KTKEGV motifs.
|
30308173 |
2018 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
These results support that Crocin is a effective inhibitor of E46K α-synuclein fibrillization and it could be considered as a potential therapeutic agent in the treatment of Parkinson disease.
|
31111370 |
2019 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Considering the potential interest of the skin as a target for the development of biomarkers in Parkinson's Disease (PD), in this work we aimed to evaluate structural and functional integrity of small autonomic nerve fibers and phosphorylated alpha-synuclein (p-synuclein) deposition in the skin of E46K-SNCA carriers as compared to those observed in parkin gene mutation (PARK2) carriers and healthy controls.
|
31178336 |
2019 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Our results suggest that C-terminal-to-N-terminal contacts in alphaS are not strongly protective against aggregation, and that the dominant mechanism by which PD-linked mutations facilitate alphaS aggregation may be altering the physicochemical properties of the protein such as net charge (E46K) and secondary structure propensity (A30P and A53T).
|
19345692 |
2009 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Mutations in the gene for α-syn, including the E46K missense mutation, are sufficient to cause Parkinson disease as well as other synucleinopathies like dementia with LBs.
|
21846727 |
2011 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Three point mutations (A30P, E46K, and A53T) as well as gene triplication genetically link the 140-residue protein alpha-synuclein (aS) to the development of Parkinson disease.
|
16166095 |
2005 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Altered ion channel formation by the Parkinson's-disease-linked E46K mutant of alpha-synuclein is corrected by GM3 but not by GM1 gangliosides.
|
20114052 |
2010 |
|
Neurodegenerative Disorders
|
|
0.010 |
GeneticVariation
|
BEFREE |
Most aSyn mutations linked to neurodegenerative disease hindered neuronal survival in this model; of these mutations, the E46K mutation proved to be the most toxic.
|
28900007 |
2017 |
|
Lewy Body Disease
|
|
0.860 |
GeneticVariation
|
BEFREE |
We examined 7 patients from a family harboring a novel mutation in the alpha-synuclein gene (E46K) that segregated with a phenotype of parkinsonism and dementia with Lewy bodies.
|
16001411 |
2005 |
|
Lewy Body Disease
|
|
0.860 |
CausalMutation
|
CLINVAR |
|
|
|
|
Lewy Body Disease
|
|
0.860 |
GeneticVariation
|
BEFREE |
Recently, a third missense mutation (E46K) in alpha-synuclein was described in an inherited form of dementia with Lewy bodies.
|
15498564 |
2004 |
|
Lewy Body Disease
|
|
0.860 |
GeneticVariation
|
UNIPROT |
The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia.
|
14755719 |
2004 |
|
Lewy Body Disease
|
|
0.860 |
GeneticVariation
|
BEFREE |
Patients with idiopathic Parkinson's disease (n = 63), dementia with Lewy bodies (n = 8), and E46K mutation carriers in the α-synuclein gene (E46K-SNCA) (n = 4) and 34 controls underwent Spectralis optical coherence tomography macular scans and a comprehensive battery of visual function and cognition tests.
|
31136022 |
2019 |
|
Lewy Body Disease
|
|
0.860 |
GeneticVariation
|
BEFREE |
The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia.
|
14755719 |
2004 |
|
Lewy Body Disease
|
|
0.860 |
GeneticVariation
|
BEFREE |
We studied 7 E46K-SNCA carriers (3 dementia with Lewy bodies, 2 pure autonomic failure, 1 PD and 1 asymptomatic), 2 PARK2 carriers and 2 healthy controls to quantify intraepidermal nerve fiber density and p-synuclein deposition with cervical skin punch biopsies (immunohistochemistry against anti PGP9.5/UCHL-1, TH and p-synuclein) and sudomotor function with electrochemical skin conductance (ESC) (SudoScan).
|
31178336 |
2019 |