ArticleACS chemical biology2010
Rescue of glaucoma-causing mutant myocilin thermal stability by chemical chaperones.
Article in ACS chemical biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed, 57 citations in OpenAlex.
- Structural basis for anomalous cellular trafficking behavior of glaucoma-associated A427T mutant myocilin.bioRxiv : the preprint server for biology · 2025Article
- Protein misfolding and mitochondrial dysfunction in glaucoma.Frontiers in cell and developmental biology · 2025Review
- Competition between inside-out unfolding and pathogenic aggregation in an amyloid-forming β-propeller.Nature communications · 2024Article
- The potential for mitochondrial therapeutics in the treatment of primary open-angle glaucoma: a review.Frontiers in physiology · 2023Review
- Quantitative differentiation of benign and misfolded glaucoma-causing myocilin variants on the basis of protein thermal stability.Disease models & mechanisms · 2023Article
- Amyloid fibrillation of the glaucoma associated myocilin protein is inhibited by epicatechin gallate (ECG).RSC advances · 2022Article
- Calcium dysregulation potentiates wild-type myocilin misfolding: implications for glaucoma pathogenesis.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2022Article
- Common and rare myocilin variants: Predicting glaucoma pathogenicity based on genetics, clinical, and laboratory misfolding data.Human mutation · 2021Review
- Molecular Insights into Myocilin and Its Glaucoma-Causing Misfolded Olfactomedin Domain Variants.Accounts of chemical research · 2021Review
- Clinically-identified C-terminal mutations in fibulin-3 are prone to misfolding and destabilization.Scientific reports · 2021Article
- Myocilin-associated Glaucoma: A Historical Perspective and Recent Research Progress.Molecular vision · 2021Review
- Different Grp94 components interact transiently with the myocilin olfactomedin domain in vitro to enhance or retard its amyloid aggregation.Scientific reports · 2019Article
- Mendelian genes in primary open angle glaucoma.Experimental eye research · 2019Review
- Calcium-ligand variants of the myocilin olfactomedin propeller selected from invertebrate phyla reveal cross-talk with N-terminal blade and surface helices.Acta crystallographica. Section D, Structural biology · 2019Article
- Stable calcium-free myocilin olfactomedin domain variants reveal challenges in differentiating between benign and glaucoma-causing mutations.The Journal of biological chemistry · 2019Article
- Mechanism of Action of VP1-001 in cryAB(R120G)-Associated and Age-Related Cataracts.Investigative ophthalmology & visual science · 2019Article
- Differential Misfolding Properties of Glaucoma-Associated Olfactomedin Domains from Humans and Mice.Biochemistry · 2019Article
- Physiological function of myocilin and its role in the pathogenesis of glaucoma in the trabecular meshwork (Review).International journal of molecular medicine · 2019Review
- Epitope mapping of commercial antibodies that detect myocilin.Experimental eye research · 2018Article
- Trifunctional High-Throughput Screen Identifies Promising Scaffold To Inhibit Grp94 and Treat Myocilin-Associated Glaucoma.ACS chemical biology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in myocilin cause an inherited form of open angle glaucoma, a prevalent neurodegenerative disorder associated with increased intraocular pressure. Myocilin forms part of the trabecular meshwork extracellular matrix presumed to regulate intraocular pressure. Missense mutations, clustered in the olfactomedin (OLF) domain of myocilin, render the protein prone to aggregation in the endoplasmic reticulum of trabecular meshwork cells, causing cell dysfunction and death. Cellular studies have demonstrated temperature-sensitive secretion of myocilin mutants, but difficulties in expression and purification have precluded biophysical characterization of wild-type (wt) myocilin and disease-causing mutants in vitro. We have overcome these limitations by purifying wt and select glaucoma-causing mutant (D380A, I477N, I477S, K423E) forms of the OLF domain (228-504) fused to a maltose binding protein (MBP) from E. coli . Monomeric fusion proteins can be isolated in solution. To determine the relative stability of wt and mutant OLF domains, we developed a fluorescence thermal stability assay without removal of MBP and provide the first direct evidence that mutated OLF is folded but less thermally stable than wt. We tested the ability of seven chemical chaperones to stabilize mutant myocilin. Only sarcosine and trimethylamine N-oxide were capable of shifting the melting temperature of all mutants tested to near that of wt OLF. Our work lays the foundation for the identification of tailored small molecules capable of stabilizing mutant myocilin and promoting secretion to the extracellular matrix, to better control intraocular pressure and to ultimately delay the onset of myocilin glaucoma.
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.