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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Erythrocyte membranes were obtained from PD patients (mutation carriers in the α-synuclein gene (A53T-PD) and glucocerebrosidase gene (GBA-PD) (n=18 each), and patients without known mutations (GU-PD, n=56)), and age-/sex-matched controls (n=56).
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29129675 |
2018 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
The PD-causing mutation A53T decreases tetramers in mouse brain.
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26076669 |
2015 |
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rs104893877
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|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
This study demonstrates that reduced GCase activity both in the context of heterozygous GBA1 mutation associated with PD and in old age, contribute to increased aggregation of mutant α-syn A53T and exacerbates the phenotype in a fly model of PD.
|
29503608 |
2018 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
A53T) are known to be directly associated with Parkinson's disease (PD).
|
28442946 |
2017 |
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rs104893877
|
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Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
FTY720 (fingolimod) reduces synucleinopathy in A53T aSyn mice and motor dysfunction in 6-OHDA and rotenone PD models, but no one has tested FTY720 in mice that develop age-onset PD-like motor problems.
|
31129200 |
2019 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
In humans, the A53T mutation induces early onset PD and increases the level of aSN oligomerization and fibrillation propensity, but Thr53 occurs naturally in aSNs of most animals.
|
30067901 |
2018 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
We failed to discover Ala53Thr or Ala30Pro mutations in a large number of Chinese patients with PD and control subjects, adding to the emerging consensus that variations in the alpha-synuclein gene are associated with PD in few families worldwide.
|
10768624 |
2000 |
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rs104893877
|
|
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 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
We have previously developed a disease-in-a-dish model for familial PD using induced pluripotent stem cells (iPSCs) from two patients carrying the p.A53T α-synuclein (αSyn) mutation.
|
30989481 |
2019 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Subjects (rat and NHP) received targeted enteric injections of PFFs or adeno-associated virus overexpressing the Parkinson's disease associated A53T α-syn mutant.
|
29341898 |
2018 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
In contrast, the naturally occurring murine A53T substitution, which is also linked to Parkinson's disease, displayed a normal membrane-binding activity that was comparable to wild-type alpha-Syn.
|
11812148 |
2002 |
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rs104893877
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Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Further investigation showed that among three single components derived from Radix Polygalae--i.e., polygalacic acid, senegenin and onjisaponin B--onjisaponin B was able to induce autophagy and accelerate both the removal of mutant huntingtin and A53T α-synuclein, which are highly associated with Huntington disease and Parkinson disease, respectively.
|
24248062 |
2013 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
The discovery of two missense mutations (A53T and A30P) in the gene encoding the presynaptic protein alpha-synuclein (alphaSN) that are genetically linked to rare familial forms of Parkinson's disease and its accumulation in Lewy bodies and Lewy neurites has triggered several attempts to generate transgenic mice overexpressing human alphaSN.
|
11113617 |
2000 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Co-expressing α-synuclein with the Parkinson's disease (PD)-associated A53T mutation and GCaMP3 in midbrain DA neurons revealed augmented cytosolic steady state and activity-dependent intra-terminal calcium levels preferentially in DLS, as well as hyperactivation and enhanced expression of N-type calcium channels.
|
30890737 |
2019 |
|
rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Dynamic Changes in Striatal mGluR1 But Not mGluR5 during Pathological Progression of Parkinson's Disease in Human Alpha-Synuclein A53T Transgenic Rats: A Multi-PET Imaging Study.
|
26758830 |
2016 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
These additional clinical and pathological features suggest that the Ala53Thr alpha-synuclein mutation can produce a more widespread disorder than found in typical idiopathic Parkinson's disease.
|
11261505 |
2001 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
The p.A53T point mutation in SNCA, the alpha-synuclein gene, has been linked to a rare dominant form of Parkinson's disease (PD).
|
28012952 |
2017 |
|
rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Controlling aggregation propensity in A53T mutant of alpha-synuclein causing Parkinson's disease.
|
19580781 |
2009 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Increased levels of wild-type (WT) alpha-synuclein (alpha-syn) and mutant A53T alpha-syn are associated with Parkinson's disease (PD), a disease linked to abnormal mitochondrial function.
|
20334438 |
2010 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Here, using a robust, patient-derived stem cell model of PD allowing comparison of A53T α-synuclein (α-syn) mutant cells and isogenic mutation-corrected controls, we identify mitochondrial toxin-induced perturbations in A53T α-syn A9 DA neurons (hNs).
|
24290359 |
2013 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Additionally, we show that either extract prolonged the survival of a PD fly model based on transgenic expression of the human α-syn A53T mutant.
|
27919712 |
2017 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Combined, these data indicate the A53T model exhibits early- and late-onset behavioral and synaptic impairments similar to PD patients and may provide useful endpoints for assessing novel therapeutic interventions for PD.
|
23936403 |
2013 |
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rs104893877
|
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Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
These models express G37R mutant Cu/Zn superoxide dismutase (SOD1G37R; fALS), A53T mutant alpha-synuclein (alpha-SynA53T; PD), full-length mutant atrophin-1-65Q, and htt-N171-82Q (huntingtin N-terminal fragment; HD).
|
17316906 |
2008 |
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rs104893877
|
|
Parkinson Disease
|
|
0.100 |
GeneticVariation
|
BEFREE |
Phosphorylation of Parkin at serine 131 by p38 MAPK promotes mitochondrial dysfunction and neuronal death in mutant A53T α-synuclein model of Parkinson's disease.
|
29899409 |
2018 |
|
rs104893877
|
|
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 |