|
Amyotrophic Lateral Sclerosis
|
0.700 |
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 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
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
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Abbreviations: ACD: alpha-crystallin domain; ALS: amyotrophic lateral sclerosis; ATG14: autophagy related 14; BAG1/3: BCL2 associated athanogene 1/3; CMT: Charcot-Marie-Tooth; dHMN: distal hereditary motor neuropathy; GFP: green fluorescent protein; HSPA8: heat shock protein family A (Hsp70) member 8; HSPB1/6/8: heat shock protein family B (small) member 1/6/8; LIR: LC3-interacting region; LC3B: microtubule associated protein 1 light chain 3 beta; PB1: Phox and Bem1; SQSTM1: sequestosome 1; STUB1/CHIP: STIP1 homology and U-box containing protein 1; UBA: ubiquitin-associated; WIPI1: WD repeat domain, phosphoinositide interacting 1; WT: wild-type.
|
30669930 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Mutations in sequestosome 1 (<i>SQSTM1</i>) gene are associated with neurodegenerative diseases, such as frontotemporal dementia and amyotrophic lateral sclerosis.
|
31525130 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Notably, mutations in the LIR-motif proteins p62 (SQSTM1) and optineurin (OPTN) contribute to familial forms of frontotemporal dementia and amyotrophic lateral sclerosis.
|
30030024 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
Disruption of the autophagic flux leads to accumulation of cytosolic protein aggregates, which are a hallmark of ALS. hiPSC-derived TBK1-mutant motoneurons (MNs) showed reduced TBK1 levels and accumulation of cytosolic SQSTM1-positive aggresomes.
|
30939964 |
2019 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
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
|
0.700 |
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
|
0.700 |
AlteredExpression
|
disease |
BEFREE |
Phospho-TDP-43-positive ALS and IBM samples also showed significant up-regulation of TARDBP and SQSTM1 expression.
|
29653597 |
2018 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
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
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Specifically, identical mutations in the autophagic adaptor SQSTM1 can cause varied penetrance of 4 distinct phenotypes: amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Paget's disease of the bone, and distal myopathy.
|
29457785 |
2018 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
Biomarker
|
disease |
BEFREE |
Previously, we have demonstrated that loss of SQSTM1 exacerbates disease phenotypes in a SOD1<sup>H46R</sup>-expressing ALS mouse model.
|
29843805 |
2018 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
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
|
0.700 |
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 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
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
|
0.700 |
Biomarker
|
disease |
BEFREE |
A large number of mutations in optineurin and optineurin-interacting proteins TANK-binding kinase (TBK1) and p62/SQSTM-1 have been found in the ALS patients, suggesting a common neuroprotective pathway.
|
28456633 |
2017 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
The present study supports previous observations on amyotrophic lateral sclerosis (ALS) that SQSTM1 mutations consistently associate with TDP-43 pathology.
|
26234378 |
2016 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
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
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Heterozygous variants in SQSTM1 have been associated with Paget disease of the bone and might contribute to neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
|
27545679 |
2016 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
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
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Here, we report that two independent ALS-linked autophagy-associated gene products; SQSTM1/p62 and ALS2/alsin, but not antioxidant-related factor; NFE2L2/Nrf2, are implicated in the pathogenesis in mutant SOD1 transgenic ALS models.
|
27439389 |
2016 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
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
|
0.700 |
GeneticVariation
|
disease |
BEFREE |
Six SQSTM1 mutations in a Chinese amyotrophic lateral sclerosis cohort.
|
25708934 |
2015 |
|
Amyotrophic Lateral Sclerosis
|
0.700 |
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
|
0.700 |
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 |