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Protein misfolding in the endoplasmic reticulum as a conduit to human disease
Abstract
In eukaryotic cells, the endoplasmic reticulum is essential for the folding and trafficking of proteins that enter the secretory pathway. Environmental insults or increased protein synthesis often lead to protein misfolding in the organelle, the accumulation of misfolded or unfolded proteins - known as endoplasmic reticulum stress - and the activation of the adaptive unfolded protein response to restore homeostasis. If protein misfolding is not resolved, cells die. Endoplasmic reticulum stress and activation of the unfolded protein response help to determine cell fate and function. Furthermore, endoplasmic reticulum stress contributes to the aetiology of many human diseases.
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“However, if the ER stress due to infection is sustained and misfolded protein cannot be refolded or degraded, the cells can also directly increase Aβ production and associated neuroinflammation80.”
From Chlamydia pneumoniae can infect the central nervous system via the olfactory and trigeminal nerves and contributes to Alzheimer’s disease risk (2022) · cites this paper as [80]
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Metadata
- Authors
- Wang, M., & Kaufman, R. J.
- Affiliations
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Kaufman, Randal J.
- Venue
- Nature
- Published
- 2016-01
- Volume
- 529
- Issue
- 7586
- Pages
- 326-335
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2263498456
- Cited by
- 1,630
- References
- 126
- Citations by year
- 2026: 127 · 2025: 166 · 2024: 177 · 2023: 180 · 2022: 200 · 2021: 179 · 2020: 185 · 2019: 137 · 2018: 120 · 2017: 113 · 2016: 44
- FWCI
- 14.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (P01CA128814, CA-128814)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK103183)
- 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 › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- protein misfolding, endoplasmic reticulum stress, unfolded protein response, secretory pathway, protein folding, protein trafficking, cell fate, human disease, ER-associated degradation
- MeSH terms
- Animals, Disease, Endoplasmic Reticulum, Humans, Proteins, Protein Folding, Unfolded Protein Response, Molecular Targeted Therapy, Endoplasmic Reticulum Stress
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