|
Frontotemporal Lobar Degeneration
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Therefore, our results reveal a mechanism whereby pathogenic SQSTM1 mutants inhibit selective autophagy and disrupt NFE2L2 anti-oxidative stress response underlying the neurotoxicity in ALS-FTLD.
|
31362587 |
2020 |
|
Frontotemporal Lobar Degeneration
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Additionally, causal relationships have been found between errors in regulation of SQSTM1/p62 and the development of a variety of neurodegenerative disorders, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and frontotemporal lobar degeneration.
|
30657305 |
2019 |
|
Frontotemporal Lobar Degeneration
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Here we report that a non-KIR domain FTLD-associated variant of p62 (p.R110C), affecting a residue close to the N-terminal PB1 oligomerisation domain, also reduces Keap1-p62 binding in cellulo and thereby reduces Nrf2 activity in reporter assays.
|
30954537 |
2019 |
|
Frontotemporal Lobar Degeneration
|
0.100 |
Biomarker
|
disease |
BEFREE |
The multifunctional protein p62 is associated with neuropathological inclusions in several neurodegenerative disorders, including frontotemporal lobar degeneration, amyotrophic lateral sclerosis and Alzheimer's disease (AD).
|
27573878 |
2017 |
|
Frontotemporal Lobar Degeneration
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Rare SQSTM1 gene mutations have been associated with Paget's disease of bone, amyotrophic lateral sclerosis, and, more recently, frontotemporal lobar degeneration (FTLD).
|
27163810 |
2016 |
|
Frontotemporal Lobar Degeneration
|
0.100 |
Biomarker
|
disease |
BEFREE |
These findings confirm a role of p62/SQSTM1 as a cause of FTLD.
|
25433461 |
2015 |
|
Frontotemporal Lobar Degeneration
|
0.100 |
Biomarker
|
disease |
BEFREE |
Frontotemporal lobar degeneration (FTLD) and motor neurone disease are linked by the possession of a hexanucleotide repeat expansion in C9ORF72, and both show neuronal cytoplasmic inclusions within cerebellar and hippocampal neurones which are TDP-43 negative but immunoreactive for p62 and dipeptide repeat proteins (DPR), these being generated by a non-ATG RAN translation of the expanded region of the gene.
|
25185840 |
2015 |
|
Frontotemporal Lobar Degeneration
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Here we consider how knowledge of the impact of PDB-associated SQSTM1 mutations (several of which are now known to be relevant for ALS/FTLD) on these pathways, as well as the locations of the mutations within the p62 primary sequence, may provide new insights into ALS/FTLD disease mechanisms.
|
24486447 |
2014 |
|
Frontotemporal Lobar Degeneration
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042).
|
24899140 |
2014 |
|
Frontotemporal Lobar Degeneration
|
0.100 |
Biomarker
|
disease |
BEFREE |
We conclude that DPR are a major component of p62 positive inclusions in FTLD and MND.
|
24252525 |
2013 |
|
Frontotemporal Lobar Degeneration
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Furthermore, 7 novel noncoding SQSTM1 variants were found in patients with FTLD and patients with ALS, including 4 variations in the promoter region.
|
22972638 |
2012 |
|
Frontotemporal Lobar Degeneration
|
0.100 |
Biomarker
|
disease |
BEFREE |
Here we immunoprecipitated endogenous p62 in the cerebral cortex from patients with frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) and found that p62 coimmunoprecipitated several proteins, including TDP-43, which is a major disease protein in FTLD-TDP.
|
22674379 |
2012 |
|
Frontotemporal Lobar Degeneration
|
0.100 |
Biomarker
|
disease |
BEFREE |
Neuropathological examination in six cases with C9ORF72 mutation from the frontotemporal lobar degeneration series identified histomorphological features consistent with either type A or B TAR DNA-binding protein-43 deposition; however, p62-positive (in excess of TAR DNA-binding protein-43 positive) neuronal cytoplasmic inclusions in hippocampus and cerebellum were a consistent feature of these cases, in contrast to the similar frequency of p62 and TAR DNA-binding protein-43 deposition in 53 control cases with frontotemporal lobar degeneration-TAR DNA-binding protein.
|
22366791 |
2012 |