|
Young onset Parkinson disease
|
|
0.010 |
GeneticVariation
|
BEFREE |
A30P and E46K are two mutants of α-synuclein (α-Syn) associated with familial early-onset Parkinson's disease (PD), and amyloid fibrils of α-Syn are the hallmarks of this disease.
|
30892349 |
2019 |
|
Small Fiber Neuropathy
|
|
0.010 |
GeneticVariation
|
BEFREE |
These results together with our previous findings support the relevance of E46K-SNCA mutation as a suitable model to study small fiber neuropathy in Lewy body diseases.
|
31178336 |
2019 |
|
Pure Autonomic Failure
|
|
0.010 |
GeneticVariation
|
BEFREE |
All E46K-SNCA carriers had moderate to severe p-synuclein deposits and small fiber neurodegeneration in different epidermal and dermal structures including nerve fascicles and glands, especially in carriers with Pure Autonomic Failure, while p-synuclein aggregates where absent in healthy controls and in one of two PARK2 carriers.
|
31178336 |
2019 |
|
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 |
|
Familial (FPAH)
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|
0.010 |
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 |
|
Dementia
|
|
0.010 |
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 |
|
Presenile dementia
|
|
0.010 |
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 |
|
Channelopathies
|
|
0.010 |
GeneticVariation
|
BEFREE |
This E46K-associated channelopathy was no longer observed when GM3 was present in phosphatidylcholine bilayers.
|
20114052 |
2010 |
|
Parkinsonian Disorders
|
|
0.010 |
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 |
|
Parkinson Disease, Familial, Type 1
|
|
0.020 |
GeneticVariation
|
BEFREE |
The only alteration identified was the p.E46K mutation in a 60-year-old man, born in Bolivia, with a familial history of autosomal dominant Parkinson's disease.
|
25817515 |
2015 |
|
Parkinson Disease, Familial, Type 1
|
|
0.020 |
GeneticVariation
|
BEFREE |
Autosomal dominant Parkinson disease (PD) is caused by duplication or triplication of the alpha-synuclein gene as well as by the A30P, E46K, and A53T mutations.The mechanisms are unknown.
|
17012252 |
2006 |
|
Parkinson Disease
|
|
0.100 |
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 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Thereby, overexpressing of α-syn-E46K mimicked a rather pre-symptomatic stage of the disease, while the α-syn-WT overexpressing animals imitated an early symptomatic stage of PD.
|
30989398 |
2019 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Here, we used an αS tetramer-abrogating mouse model of PD (3K) that amplifies the familial E46K PD mutation to investigate the effects of female sex and brain-selective estrogen treatment on αS tetramerization and solubility, formation of vesicle-rich αS<sup>+</sup> aggregates, dopaminergic and cortical fiber integrity, and associated motor deficits.
|
31405930 |
2019 |
|
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 |
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 |
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 |
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 |
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 |
An αS '3K' mutant (E35K + E46K + E61K) that amplifies the PD/DLB-causing E46K mutation induced αS-rich vesicle clusters resembling the vesicle-rich areas of Lewy bodies, supporting pathogenic relevance.
|
28911198 |
2017 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Finally, we observed that the PD-linked mutation E46K enhances PLK2-mediated α-syn degradation, suggesting that this mutated form is a <i>bona fide</i> substrate of this degradation pathway.
|
28154193 |
2017 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Parkinson disease mutant E46K enhances α-synuclein phosphorylation in mammalian cell lines, in yeast, and in vivo.
|
25657004 |
2015 |
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Our findings add new insight into the preexisting information about α-synuclein p.E46K, improving our understanding about the endophenotypes associated to this mutation and corroborate that missense alterations and multiplications in α-synuclein are uncommon among Brazilian patients with Parkinson's disease.
|
25817515 |
2015 |