A molecular chaperone inducer protects neurons from ER stress
Open accessAbstract
The endoplasmic reticulum (ER) stress response is a defense system for dealing with the accumulation of unfolded proteins in the ER lumen. Recent reports have shown that ER stress is involved in the pathology of some neurodegenerative diseases and cerebral ischemia. In a screen for compounds that induce the ER-mediated chaperone BiP (immunoglobulin heavy-chain binding protein)/GRP78 (78 kDa glucose-regulated protein), we identified BiP inducer X (BIX). BIX preferentially induced BiP with slight inductions of GRP94 (94 kDa glucose-regulated protein), calreticulin, and C/EBP homologous protein. The induction of BiP mRNA by BIX was mediated by activation of ER stress response elements upstream of the BiP gene, through the ATF6 (activating transcription factor 6) pathway. Pretreatment of neuroblastoma cells with BIX reduced cell death induced by ER stress. Intracerebroventricular pretreatment with BIX reduced the area of infarction due to focal cerebral ischemia in mice. In the penumbra of BIX-treated mice, ER stress-induced apoptosis was suppressed, leading to a reduction in the number of apoptotic cells. Considering these results together, it appears that BIX induces BiP to prevent neuronal death by ER stress, suggesting that it may be a potential therapeutic agent for cerebral diseases caused by ER stress.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Increased ROS can have detrimental effects in neuronal cells, resulting in endoplasmic reticulum stress as proteins are miss-folded and mitochondrial stress and leakage, which can cause apoptosis and neurodegeneration.
“Increased ROS can have many detrimental effects in neuronal cells, resulting in endoplasmic reticulum stress, as proteins are miss-folded4 and mitochondrial stress and leakage, which can cause apoptosis and neurodegeneration.5”
From Bacopa monnieri (L.) wettst. Extract protects against glutamate toxicity and increases the longevity of Caenorhabditis elegans (2020) · cites this paper as [4]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 28 · Cited by 250
- Authors
- Kudo, T., Kanemoto, S., Hara, H., Morimoto, N., Morihara, T., Kimura, R., Tabira, T., Imaizumi, K., & Takeda, M.
- Affiliations
- The University of Osaka (JP)
- University of Miyazaki (JP)
- Gifu Pharmaceutical University (JP)
- Corresponding author
- Kudo, T
- Imaizumi, K
- Venue
- Cell Death & Differentiation
- Published
- 2007-11-30
- Volume
- 15
- Issue
- 2
- Pages
- 364-375
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- OpenAlex
- W1989347991
- Cited by
- 250
- References
- 28
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 3 · 2023: 15 · 2022: 15 · 2021: 13 · 2020: 8 · 2019: 16 · 2018: 9 · 2017: 16 · 2016: 24 · 2015: 13 · 2014: 14 · 2013: 15 · 2012: 18
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Death and Differentiation (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of Biomedical Innovation
- Japan Society for the Promotion of Science (17200026)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- endoplasmic reticulum stress, BiP/GRP78, GRP94, calreticulin, C/EBP homologous protein, ATF6 pathway, neuroprotection, neuronal apoptosis, cerebral ischemia, neurodegenerative diseases, unfolded protein accumulation, ER stress response element
- MeSH terms
- Endoplasmic Reticulum Chaperone BiP, Animals, Cerebral Infarction, Endoplasmic Reticulum, Heat-Shock Proteins, Humans, Membrane Proteins, Neurons, Thiocyanates, Apoptosis, Mice, Knockout, Oxidative Stress, Molecular Chaperones, HSP70 Heat-Shock Proteins, Cell Line, Tumor, Mice, Activating Transcription Factor 6
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
