AMYOTROPHIC LATERAL SCLEROSIS 18
|
0.700 |
GeneticVariation
|
disease |
UNIPROT |
Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis.
|
22801503 |
2012 |
AMYOTROPHIC LATERAL SCLEROSIS 18
|
0.700 |
Biomarker
|
disease |
GENOMICS_ENGLAND |
Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis.
|
22801503 |
2012 |
AMYOTROPHIC LATERAL SCLEROSIS 18
|
0.700 |
Biomarker
|
disease |
CTD_human |
|
|
|
AMYOTROPHIC LATERAL SCLEROSIS 18
|
0.700 |
CausalMutation
|
disease |
CLINVAR |
|
|
|
Amyotrophic Lateral Sclerosis
|
0.500 |
Biomarker
|
disease |
BEFREE |
In silico analysis of PFN1 related to amyotrophic lateral sclerosis.
|
31216283 |
2019 |
Amyotrophic Lateral Sclerosis
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Although profilin 1 C71G was only expressed during development, adult mice presented with some ALS-associated pathology and motor symptoms.
|
31611772 |
2019 |
Amyotrophic Lateral Sclerosis
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Recently, we developed a mouse model for ALS using a PFN1 mutation (glycine 118 to valine, G118V), and we are now interested in understanding how PFN1 becomes toxically lethal with only one amino acid substitution.
|
30203378 |
2018 |
Amyotrophic Lateral Sclerosis
|
0.500 |
Biomarker
|
disease |
BEFREE |
Thirty individuals with ALS (18 men and 12 women, mean age 59 years, range 44-74 years) with a mean score of 26, (minimum score of 14 and maximum 41) on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and 30 healthy controls matched for age and gender, participated.
|
30558556 |
2018 |
Amyotrophic Lateral Sclerosis
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
In this study, we investigated the structural perturbations of PFN1 caused by each ALS-associated mutation.
|
30166578 |
2018 |
Amyotrophic Lateral Sclerosis
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
A set of missense mutations in the gene encoding profilin-1 has been linked to the onset of familial forms of ALS (fALS), also known as Lou Gehrig's disease.
|
29760185 |
2018 |
Amyotrophic Lateral Sclerosis
|
0.500 |
AlteredExpression
|
disease |
BEFREE |
One of the mouse lines expressing high levels of mutant human PFN1 protein in the brain and spinal cord exhibited many key clinical and pathological features consistent with human ALS disease.
|
28040732 |
2017 |
Amyotrophic Lateral Sclerosis
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Our results imply that one potential mechanism for C71G-PFN1 to initiate ALS might be the abnormal interaction with membranes as recently established for SOD1 mutants.
|
28847504 |
2017 |
Amyotrophic Lateral Sclerosis
|
0.500 |
Biomarker
|
disease |
BEFREE |
Five structurally and functionally different proteins, an enzyme superoxide dismutase 1 (SOD1), a TAR-DNA binding protein-43 (TDP-43), an RNA-binding protein FUS, a cofilin-binding protein C9orf72, and polypeptides generated as a result of its intronic hexanucleotide expansions, and to lesser degree actin-binding profilin-1 (PFN1), are considered to be the major drivers of amyotrophic lateral sclerosis.
|
27838743 |
2017 |
Amyotrophic Lateral Sclerosis
|
0.500 |
Biomarker
|
disease |
BEFREE |
Pathological developments leading to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are associated with misbehavior of several key proteins, such as SOD1 (superoxide dismutase 1), TARDBP/TDP-43, FUS, C9orf72, and dipeptide repeat proteins generated as a result of the translation of the intronic hexanucleotide expansions in the C9orf72 gene, PFN1 (profilin 1), GLE1 (GLE1, RNA export mediator), PURA (purine rich element binding protein A), FLCN (folliculin), RBM45 (RNA binding motif protein 45), SS18L1/CREST, HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1), HNRNPA2B1 (heterogeneous nuclear ribonucleoprotein A2/B1), ATXN2 (ataxin 2), MAPT (microtubule associated protein tau), and TIA1 (TIA1 cytotoxic granule associated RNA binding protein).
|
28980860 |
2017 |
Amyotrophic Lateral Sclerosis
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Here, we investigated direct effects of profilin on microtubule dynamics and whether ALS-linked mutations in PFN1 disrupt such functions.
|
29129529 |
2017 |
Amyotrophic Lateral Sclerosis
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Co-expression of ALS-linked mutant PFN1 and TDP-43 increased insoluble and phosphorylated TDP-43 levels.
|
26908597 |
2016 |
Amyotrophic Lateral Sclerosis
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Knockdown of endogenous Drosophila PFN1 did not alter the degenerative phenotypes of the retina in flies overexpressing wild-type TDP-43 These data suggest that ALS-linked PFN1 mutations exacerbate TDP-43-induced neurodegeneration in a gain-of-function manner, possibly by shifting the localization of TDP-43 from nuclei to cytoplasm.
|
27634045 |
2016 |
Amyotrophic Lateral Sclerosis
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Moreover, detergent-insoluble fractions prepared from cells expressing ALS-linked mutant PFN1 induced seed-dependent accumulation of TDP-43.
|
27432186 |
2016 |
Amyotrophic Lateral Sclerosis
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Biophysical analysis of three novel profilin-1 variants associated with amyotrophic lateral sclerosis indicates a correlation between their aggregation propensity and the structural features of their globular state.
|
27101547 |
2016 |
Amyotrophic Lateral Sclerosis
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
PFN1 is a small actin-binding protein that promotes formin-based actin polymerization and regulates numerous cellular functions, but how the mutations in PFN1 cause ALS is unclear.
|
27681617 |
2016 |
Amyotrophic Lateral Sclerosis
|
0.500 |
Biomarker
|
disease |
BEFREE |
These findings suggest that a destabilized form of PFN1 underlies PFN1-mediated ALS pathogenesis.
|
26056300 |
2015 |
Amyotrophic Lateral Sclerosis
|
0.500 |
Biomarker
|
disease |
BEFREE |
Our findings show that PFN1 is a rare cause of ALS and adds further weight to the underlying genetic heterogeneity of this disease.
|
25499087 |
2015 |
Amyotrophic Lateral Sclerosis
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
In this study we show that expression of the ALS-associated actin-binding deficient mutant of PFN1 (PFN1(C71G)) results in increased dendritic arborisation and spine formation, and cytoplasmic inclusions in cultured mouse hippocampal neurons.
|
26499959 |
2015 |
Amyotrophic Lateral Sclerosis
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Mutations of Profilin-1 Associated with Amyotrophic Lateral Sclerosis Promote Aggregation Due to Structural Changes of Its Native State.
|
26226631 |
2015 |
Amyotrophic Lateral Sclerosis
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Impaired actin binding is a common denominator of several PFN1 mutations associated with amyotrophic lateral sclerosis, although further mechanisms may also contribute to the death of motor neurons.
|
26572741 |
2015 |