ArticleBiochimica et biophysica acta. Molecular basis of disease2022
Amyloid aggregates exert cell toxicity causing irreversible damages in the endoplasmic reticulum.
Article in Biochimica et biophysica acta. Molecular basis of disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 39 citations in OpenAlex.
- Changes in the concentration of phosphatidylcholine in lipid bilayers determines the aggregation rate of transthyretin.Biophysical chemistry · 2026Article
- Microglial lipid droplets as therapeutic targets in age-related neurodegenerative diseases.npj aging · 2025Review
- Leveraging bioorthogonal conjugation for alpha synuclein fibril surveillance.bioRxiv : the preprint server for biology · 2025Article
- Elucidation of cytotoxicity of α-Synuclein fibrils on immune cells.Biochimica et biophysica acta. Proteins and proteomics · 2025Article
- Tubulin-Binding Region Modulates Cholesterol-Triggered Aggregation of Tau Proteins.Journal of neurochemistry · 2025Article
- Elucidation of molecular mechanisms by which amyloid βBiochimica et biophysica acta. Molecular and cell biology of lipids · 2024Article
- Macrophages and Natural Killers Degrade α-Synuclein Aggregates.Molecular pharmaceutics · 2024Article
- Length and saturation of choline plasmalogens alter the aggregation rate of α-synuclein but not the toxicity of amyloid fibrils.International journal of biological macromolecules · 2024Article
- Melatonin protects against defects induced by methoxychlor in porcine oocyte maturation.Cell cycle (Georgetown, Tex.) · 2024Article
- Secondary structure and toxicity of lysozyme fibrils are determined by the length and unsaturation of phosphatidic acid.Proteins · 2024Article
- The influence of zwitterionic and anionic phospholipids on protein aggregation.Biophysical chemistry · 2024Review
- Long-Chain Polyunsaturated Fatty Acids Accelerate the Rate of Insulin Aggregation and Enhance Toxicity of Insulin Aggregates.ACS chemical neuroscience · 2024Article
- Deactivation of the Unfolded Protein Response Aggravated Renal AA Amyloidosis in HSF1 Deficiency Mice.Molecular and cellular biology · 2024Article
- Cholesterol and Sphingomyelin Uniquely Alter the Rate of Transthyretin Aggregation and Decrease the Toxicity of Amyloid Fibrils.The journal of physical chemistry letters · 2023Article
- Nano-infrared analysis of amyloid βNanoscale · 2023Article
- Nanoscale structural characterization of transthyretin aggregates formed at different time points of protein aggregation using atomic force microscopy-infrared spectroscopy.Protein science : a publication of the Protein Society · 2023Article
- Elucidating the Role of Lipids in the Aggregation of Amyloidogenic Proteins.Accounts of chemical research · 2023Article
- Saturation of fatty acids in phosphatidic acid uniquely alters transthyretin stability changing morphology and toxicity of amyloid fibrils.Chemistry and physics of lipids · 2023Article
- Elucidation of the Role of Lipids in Late Endosomes on the Aggregation of Insulin.ACS chemical neuroscience · 2023Article
- Role of Saturation and Length of Fatty Acids of Phosphatidylserine in the Aggregation of Transthyretin.ACS chemical neuroscience · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Amyloid oligomers and fibrils are protein aggregates that cause an onset and progression of many neurodegenerative diseases, diabetes type 2 and systemic amyloidosis. Although a growing body of evidence shows that oligomers and fibrils trigger mitochondrial dysfunction simultaneously enhancing production of reactive oxygen species, exact mechanisms by which these protein aggregates exert their toxicities remain unclear. In this study, we used advanced microscopic and spectroscopic methods to examine topography and structure of insulin aggregates grown in the lipid-free environment, as well as in the presence of major classes of phospho- and sphingolipids. We also employed a set of molecular markers to determine the extent to which insulin aggregates induce a damage of cell endoplasmic reticulum (ER), an important cell organelle used for calcium storage, protein synthesis and folding. Our results show that insulin aggregates activate the expression of Activating Transcription Factor 6 (ATF6), a transmembrane protein that is involved in unfolded protein response (UPR) of the stressed ER. At the same time, two other ER transmembrane proteins, Inositol Requiring 1 (IRE1α) and eLF2a, the product of PKR-like ER kinase (PERK), exhibited very low expression levels. Furthermore, amyloid aggregates trigger an expression of the 78-kDa glucose-regulated protein GRP78, which is also involved in the UPR. We also observed UPR-induced expression of a proapoptotic transcription factor CHOP, which, in turn, regulates expression of caspase 3 kinase and BCL2 protein family members, including the ER localized Bax. These findings show that insulin oligomers and fibrils induce UPR-associated ER stress and ultimately fatal changes in cell homeostasis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.