|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
HPO |
|
|
|
|
Frontotemporal dementia
|
0.200 |
AlteredExpression
|
disease |
BEFREE |
<b>Abbreviations:</b> 4HPR: 4-hydroxy(phenyl)retinamide; AKT: AKT1 serine/threonine kinase 1; ALS: amyotrophic lateral sclerosis; ATG: autophagy related; AVs: autophagic vesicle; C9orf72: chromosome 9 open reading frame 72; CASP3: caspase 3; CHAT: choline O-acetyltransferase; CYCS: cytochrome c, somatic; DIV: day in vitro; FTD: frontotemporal dementia; FUS: FUS RNA binding protein; GFP: green fluorescent protein; hiPSCs: human induced pluripotent stem cells; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MNs: motoneurons; mRFP: monomeric red fluorescent protein; MTOR: mechanistic target of rapamycin kinase; NFE2L2/NRF2: nuclear factor, erythroid 2 like 2; RARA: retinoic acid receptor alpha; SLC18A3/VACHT: solute carrier family 18 (vesicular acetylcholine transporter), member 3; SQSTM1/p62: sequestosome 1; TBK1: TANK binding kinase 1; TEM: transmission electron microscopy.
|
30939964 |
2019 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
FTD is pathologically heterogeneous, both macroscopically and on a molecular level, with tau positive, TDP-43 positive, and FUS positive intraneuronal inclusions recognized on immunohistochemical analysis.
|
20413882 |
2010 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
FTD usually belongs to the frontotemporal lobar degeneration (FTLD) disease group, and its familial forms are dominantly inherited and linked to a group of genes relevant to frontal and temporal brain pathology, such as MAPT, GRN, C9ORF72, TARDBP, CHMP2B, VCP, and FUS.
|
29578490 |
2018 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
FUS/TLS (fused in sarcoma/translocated in liposarcoma) and TDP-43 are integrally involved in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.
|
23023293 |
2012 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
Fused-in-sarcoma (FUS) is a nuclear protein linked to amyotrophic lateral sclerosis and frontotemporal dementia.
|
25192599 |
2015 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
FUS (fused in sarcoma) mislocalization and cytoplasmic aggregation are hallmark pathologies in FUS-related amyotrophic lateral sclerosis and frontotemporal dementia.
|
29194538 |
2018 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
A combination of whole-exome sequencing, Sanger sequencing and fragment analysis/Southern blot was performed in order to identify pathogenic mutations and novel variants in these genes as well as other FTD-related genes such as the 'charged multivesicular body protein 2B' (CHMP2B), the 'FUS RNA binding protein' (FUS), the 'TAR DNA binding protein' (TARDBP), the 'sequestosome1' (SQSTM1), and the 'valosin containing protein' (VCP).
|
27632209 |
2016 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
A significant increase of Fe deposition was observed in the claustrum, caudate nucleus, globus pallidus, thalamus, and subthalamic nucleus of the FTLD-FUS and FTLD-TDP groups, while in the ALS one, the Fe increase was only observed in the caudate and the subthalamic nuclei.
|
28988390 |
2017 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
Accumulation of tau, TDP-43 or FUS cytoplasmic aggregates characterize molecularly distinct and non-overlapping FTD subtypes.
|
27502124 |
2016 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
Additionally, we identified 2 previously reported heterozygous insertion and deletion mutations in Exon 5 of FUS; Gly174-Gly175 del GG (g. 4180-4185 delGAGGTG) in an FTD patient and Gly175-Gly176 ins GG (g. 4185-4186 insGAGGTG) in a patient with diagnosis of CBS.
|
21943958 |
2012 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
Aggregation of fused in sarcoma (FUS) protein, and mutations in FUS gene, are causative to a range of neurodegenerative disorders including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia.
|
29425337 |
2018 |
|
Frontotemporal dementia
|
0.200 |
PosttranslationalModification
|
disease |
BEFREE |
ALS-associated FUS-NLS mutations weaken the chaperone activity of Transportin and loss of FUS arginine methylation, as seen in FTD-FUS, promote phase separation, and stress granule partitioning of FUS.
|
29677514 |
2018 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
Although these findings provide further support for the concept that ALS and FTD are closely related clinical syndromes with an overlapping molecular basis, important differences in the pathological features and results from experimental models indicate that ALS-<i>FUS</i> and FTLD-FUS have distinct pathogenic mechanisms.
|
28096243 |
2017 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
Collectively, our evidence demonstrates that human ALS/FTD-linked mutations in FUS induce a gain of toxicity that includes stress-mediated suppression in intra-axonal translation, synaptic dysfunction, and progressive age-dependent motor and cognitive disease without cytoplasmic aggregation, altered nuclear localization, or aberrant splicing of FUS-bound pre-mRNAs.VIDEO ABSTRACT.
|
30344044 |
2018 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
Dysregulation of RNA metabolism represents an important pathogenetic mechanism in both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) due to the involvement of the DNA/RNA-binding proteins TDP-43 and FUS and, more recently, of C9ORF72.
|
27151080 |
2016 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
FALS patients with C9ORF72 expansions had more frequent association with FTD than the other FALS patients (p<0.0001 vs SOD1, p=0.04 vs TARDBP, p=0.004 vs FUS, p=0.03 vs other FALS).
|
22499346 |
2012 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
Genetic mutations in RNA-binding proteins FUS and TDP-43 have been linked with causing neurodegenerative diseases: amyotrophic lateral sclerosis and frontotemporal dementia.
|
26047658 |
2015 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
Hence, the spatial patterns of the NCI were compared in three molecular subtypes of FTLD: (1) two variants of FTLD-tau, viz. cortico-basal degeneration (CBD) and Pick's disease (PiD), (2) FTLD with transactive response (TAR) DNA-binding protein 43(TDP-43)-immunoreactive inclusions (FTLD-TDP), and (3) FTLD with 'fused in sarcoma' (FUS)-immunoreactive inclusions (FTLD-FUS).
|
28984110 |
2017 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
Here, we discuss the evidence for FUS pathogenicity in ALS/FTD, review the experimental approaches used and phenotypic features of FUS rodent models reported to date, and outline their contribution to our understanding of pathogenic mechanisms.
|
27600654 |
2016 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
In addition to familial ALS, abnormal aggregates of FUS are present in a portion of FTD and other neurodegenerative diseases independent of their mutations.
|
31230528 |
2019 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
In fact, it has been demonstrated that lncRNAs are dysregulated upon either depletion or unavailability of functional TDP-43 or FUS/TLS in a range of different models and diseases, including post-mortem samples from subjects with FTLD-TDP.
|
26220395 |
2015 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
In the case of ALS and FTD, these protein aggregates are found in the cytoplasm of affected neurons and contain certain RNA-binding proteins (RBPs), namely the TAR DNA-binding protein of 43 kDa (TDP-43) and the fused in sarcoma (FUS) gene product.
|
30486313 |
2018 |
|
Frontotemporal dementia
|
0.200 |
GeneticVariation
|
disease |
BEFREE |
Inclusions containing Fused in Sarcoma (FUS) are found in familial and sporadic cases of the incurable progressive motor neuron disease amyotrophic lateral sclerosis and in a common form of dementia, frontotemporal dementia.
|
25447237 |
2015 |
|
Frontotemporal dementia
|
0.200 |
Biomarker
|
disease |
BEFREE |
Intriguingly, many of the RNA targets of TDP-43 and FUS are involved in synaptic transmission and plasticity, indicating that synaptic dysfunction could be an early event contributing to motor and cognitive deficits in ALS and FTD.
|
29755516 |
2018 |