Derlin-1 overexpression ameliorates mutant SOD1-induced endoplasmic reticulum stress by reducing mutant SOD1 accumulation

Mori, Akira; Yamashita, Satoshi; Uchino, Katsuhisa; Suga, Tomohiro; Ikeda, Tokunori; Takamatsu, Koutaro; Ishizaki, Masatoshi; Koide, Tatsuya; Kimura, En; Mita, Shuji; Maeda, Yasushi; Hirano, Teruyuki; Uchino, Makoto

doi:10.1016/j.neuint.2010.12.010

Cited by 34 publications

(20 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…that Derlin-1, which is involved in retrotranslocation of misfolded proteins across the ER membrane for purposes of degradation, can trigger ER stress owing to its interaction with mutant SOD1 [53]. Furthermore, the BH3-only protein, Bim has been directly linked to ER stress and the ensuing mitochondrial apoptosis in the murine neuroblastoma cell line, Neuro2a [54].…”

Section: Protein Misfolding and Er Stress In Alsmentioning

confidence: 99%

Calcium-dependent protein folding in amyotrophic lateral sclerosis

2013

View full text Add to dashboard Cite

Section: Protein Misfolding and Er Stress In Alsmentioning

confidence: 99%

Calcium-dependent protein folding in amyotrophic lateral sclerosis

2013

View full text Add to dashboard Cite

“…Autotaxin (ATX) is a secreted lysophospholipase D that converts lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a phospholipid growth factor that activates several transduction pathways, and is involved in migration, proliferation, and survival of various cells (Mori et al, 2011; Furukawa et al, 2013). LPA acts as an autocrine and/or paracrine signaling molecule mediating a broad range of intracellular signaling cascades, especially the RHOA pathway (reviewed in Willier et al, 2011).…”

Section: Neurodegenerative Networking In Alsmentioning

confidence: 99%

Microglia centered pathogenesis in ALS: insights in cell interconnectivity

Brites

Vaz

2014

Front. Cell. Neurosci.

170

126

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is the most common and most aggressive form of adult motor neuron (MN) degeneration. The cause of the disease is still unknown, but some protein mutations have been linked to the pathological process. Loss of upper and lower MNs results in progressive muscle paralysis and ultimately death due to respiratory failure. Although initially thought to derive from the selective loss of MNs, the pathogenic concept of non-cell-autonomous disease has come to the forefront for the contribution of glial cells in ALS, in particular microglia. Recent studies suggest that microglia may have a protective effect on MN in an early stage. Conversely, activated microglia contribute and enhance MN death by secreting neurotoxic factors, and impaired microglial function at the end-stage may instead accelerate disease progression. However, the nature of microglial–neuronal interactions that lead to MN degeneration remains elusive. We review the contribution of the neurodegenerative network in ALS pathology, with a special focus on each glial cell type from data obtained in the transgenic SOD1G93A rodents, the most widely used model. We further discuss the diverse roles of neuroinflammation and microglia phenotypes in the modulation of ALS pathology. We provide information on the processes associated with dysfunctional cell–cell communication and summarize findings on pathological cross-talk between neurons and astroglia, and neurons and microglia, as well as on the spread of pathogenic factors. We also highlight the relevance of neurovascular disruption and exosome trafficking to ALS pathology. The harmful and beneficial influences of NG2 cells, oligodendrocytes and Schwann cells will be discussed as well. Insights into the complex intercellular perturbations underlying ALS, including target identification, will enhance our efforts to develop effective therapeutic approaches for preventing or reversing symptomatic progression of this devastating disease.

show abstract

“…Derlin-1 can relieve ER stress-induced apoptosis in breast cancer cells [8]. Derlin-1 overexpression also ameliorates mutant superoxide dismutase 1 (SOD1)-induced ER stress and cell toxicity by reducing mutant SOD1 accumulation [9]. The role of Derlin-1 has also been implicated in human cancers.…”

Section: Introductionmentioning

confidence: 99%

Derlin-1 overexpression confers poor prognosis in muscle invasive bladder cancer and contributes to chemoresistance and invasion through PI3K/AKT and ERK/MMP signaling

Dong

Zhao

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Derlin-1 has been found to be overexpressed in several human cancers. However, its clinical significance and biological roles in bladder cancer remain unexplored. Here, we found that Derlin-1 was upregulated in 38.6% (58/150) cases of cancer samples. The rate of Derlin-1 overexpression was higher in muscle invasive bladder cancer (MIBC) than non-muscle invasive bladder cancer (NMIBC) (p=0.0079). Derlin-1 was a predicting factor for poor patient prognosis. Derlin-1 depletion inhibited while its overexpression facilitated cell invasion and colony formation. In addition, Derlin-1 overexpression induced cisplatin resistance while its depletion sensitized cancer cells to cisplatin. Further analysis demonstrated that Derlin-1 activated AKT phosphorylation and upregulated Bcl-2 expression. Blockage of AKT signaling by LY294005 abolished the effects of Derlin-1 on Bcl-2 and cisplatin resistance. Immunoprecipitation indicated Derlin-1 interacted with p110α subunit of PI3K. In addition, we showed that Derlin-1 depletion downregulated and its overexpression upregulated cell MMP-2/9 expression and ERK phosphorylation. Derlin-1 mediated upregulation of MMP-2/9 could be blocked by ERK inhibitor. In conclusion, our study demonstrated that Derlin-1 is overexpressed in bladder cancer and promotes malignant phenotype through ERK/MMP and PI3K/AKT/Bcl-2 signaling pathway.

show abstract

Derlin-1 overexpression ameliorates mutant SOD1-induced endoplasmic reticulum stress by reducing mutant SOD1 accumulation

Cited by 34 publications

References 18 publications

Calcium-dependent protein folding in amyotrophic lateral sclerosis

Calcium-dependent protein folding in amyotrophic lateral sclerosis

Microglia centered pathogenesis in ALS: insights in cell interconnectivity

Derlin-1 overexpression confers poor prognosis in muscle invasive bladder cancer and contributes to chemoresistance and invasion through PI3K/AKT and ERK/MMP signaling

Contact Info

Product

Resources

About