|
Alzheimer's Disease
|
0.100 |
Biomarker
|
disease |
BEFREE |
We performed immunohistochemical tests for the presence of S403-phos-p62 in postmortem brain of neurodegenerative disease cases, and found accumulations in amyotrophic lateral sclerosis and Alzheimer's disease tissues.
|
26302676 |
2016 |
|
Alzheimer's Disease
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Recently we reported that declined SQSTM1/p62 expression in Alzheimer disease brain was age-correlated with oxidative damage to the p62 promoter.
|
19481605 |
2009 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
TBK1 is known to bind to and phosphorylate a number of proteins involved in innate immunity and autophagy, including optineurin (OPTN) and p62 (SQSTM1/sequestosome), both of which have also been implicated in ALS.
|
25700176 |
2015 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
We performed a systematic review on 42 pathological studies to assess the pooled prevalence rates and density (a measure of the number of inclusions per brain region) of (phosphorylated)-TDP-43, p62 and DRP neuronal inclusions in seven brain regions and the spinal cord of 261 C9ORF72-positive patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and ALS-FTD.
|
26373655 |
2016 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our results suggest a difference in HR23B aggregation and co-localization pattern with DPRs, pTDP-43 and p62 between different brain areas from C9FTD/ALS cases.
|
30867060 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
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 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
SQSTM1 mutations, coding for the p62 protein, were identified as a monogenic cause of Paget disease of bone and of amyotrophic lateral sclerosis.
|
25114083 |
2015 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Recently, mutations in the sequestosome 1 (SQSTM1) gene, which encodes p62 protein, have been reported in patients with ALS.
|
22972638 |
2012 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Previously, two ALS-FTLD-associated p62 mutant proteins within the Keap1 interacting region (KIR) of p62 were found to be associated with decreased Keap1-p62 binding and Nrf2 activation.
|
30954537 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
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 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Mutations in the gene encoding p62 in Japanese patients with amyotrophic lateral sclerosis.
|
23303844 |
2013 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Interestingly, we report for the first time pathological hallmarks of SPG11 in neurons that include intracytoplasmic granular lysosome-like structures mainly in supratentorial areas, and others in subtentorial areas that are partially reminiscent of those observed in amyotrophic lateral sclerosis, such as ubiquitin and p62 aggregates, except that they are never labelled with anti-TDP-43 or anti-cystatin C. The neuropathological overlap with amyotrophic lateral sclerosis, associated with some shared clinical manifestations, opens up new fields of investigation in the physiopathological continuum of motor neuron degeneration.
|
27016404 |
2016 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Our findings provide evidence of a direct genetic role for p62 in ALS pathogenesis and suggest that regulation of protein degradation pathways may represent an important therapeutic target in motor neuron degeneration.
|
22084127 |
2011 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Accumulating evidence suggests that heterozygous mutations in the SQSTM1 gene, which encodes p62 protein, are associated with amyotrophic lateral sclerosis (ALS).
|
23812289 |
2013 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Furthermore, we found elevated levels of high molecular weight ubiquitinated proteins and p62 in animals expressing ALS-causing genes with TBI, suggesting that TBI may lead to the defects in protein degradation pathways.
|
29432563 |
2018 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
We performed immunohistochemical tests for the presence of S403-phos-p62 in postmortem brain of neurodegenerative disease cases, and found accumulations in amyotrophic lateral sclerosis and Alzheimer's disease tissues.
|
26302676 |
2016 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Remarkably, despite the large degree of heterogeneity, all cases of ALS have protein aggregates in the brain and spinal cord that are immunopositive for SOD1, TDP-43, OPTN, and/or p62.
|
29515358 |
2018 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Post-mortem analysis of p62 is a defining diagnostic marker in several neurodegenerative diseases including amyotrophic lateral sclerosis and inclusion body myositis.
|
28076378 |
2017 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
These mutations that are located in the ubiquitin-associated domain (UBA domain) of the p62 protein have already been described in Paget's disease and ALS patients carrying these mutations had both concomitant Paget's disease.
|
23417734 |
2013 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
α-Synuclein and p62 immunohistochemistry of the substantia nigra (SN) was undertaken in brains of 17 ALS cases with (C9ORF72+) and 51 without (C9ORF72-) the C9ORF72 expansion.
|
23884045 |
2013 |
|
Amyotrophic Lateral Sclerosis
|
0.100 |
Biomarker
|
disease |
BEFREE |
Mutations in the p62 gene (also known as SQSTM1) which encodes the p62 protein have been reported in both disorders supporting the idea of an ALS/FTD continuum.
|
28490746 |
2017 |
|
Cholangitis, Sclerosing
|
0.100 |
GeneticVariation
|
disease |
GWASCAT |
Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis.
|
28779025 |
2018 |
|
Biliary cirrhosis
|
0.100 |
Biomarker
|
disease |
HPO |
|
|
|
|
Osteitis Deformans
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
To further clarify the functional impact of p62 mutations associated with PDB, we assessed the effect of p62 mutation (a novel mutation: K378X, and previously reported mutations: P392L and E396X) on RANK-induced NF-kappaB activation and compared this with the effect of wildtype p62.
|
16813535 |
2006 |
|
Osteitis Deformans
|
0.100 |
Biomarker
|
disease |
BEFREE |
Thus, phenotypically identical substitution and deletion mutations do not appear to predispose to PDB through a mechanism dependent on a common loss of ubiquitin chain binding by p62.
|
12857745 |
2003 |