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View article: DOP132 An integrated single-cell atlas enables the discovery and validation of a novel candidate therapeutic target for Inflammatory Bowel Disease
DOP132 An integrated single-cell atlas enables the discovery and validation of a novel candidate therapeutic target for Inflammatory Bowel Disease Open
Background Single-cell technologies enable the fine mapping of disease and treatment mechanisms in inflammatory bowel disease (IBD). We sought to leverage these insights to discover novel drug targets with precise therapeutic hypotheses. T…
View article: DOP40 Inflammatory Bowel Disease single cell atlas construction to enable cell type-specific target identification
DOP40 Inflammatory Bowel Disease single cell atlas construction to enable cell type-specific target identification Open
Background Advances in single-cell technologies enable the unbiased study of cellular heterogeneity. Recently, single-cell RNA sequencing (scRNA-seq) has been utilised on intestinal and blood samples from patients with inflammatory bowel d…
View article: Reduced Levels of Misfolded and Aggregated Mutant p53 by Proteostatic Activation
Reduced Levels of Misfolded and Aggregated Mutant p53 by Proteostatic Activation Open
In malignant cancer, excessive amounts of mutant p53 often lead to its aggregation, a feature that was recently identified as druggable. Here, we describe that induction of a heat shock-related stress response mediated by Foldlin, a small-…
View article: The tumor suppressor protein PTEN undergoes amyloid-like aggregation in tumor cells
The tumor suppressor protein PTEN undergoes amyloid-like aggregation in tumor cells Open
Protein aggregation is an underappreciated mechanism that may contribute to the loss- and oncogenic-gain-of-function of mutant tumor suppressors such as p53 and axin. In the present study, we describe amyloid-like aggregation behaviour of …
View article: Exposure of a cryptic Hsp70 binding site determines the cytotoxicity of the ALS-associated SOD1-mutant A4V
Exposure of a cryptic Hsp70 binding site determines the cytotoxicity of the ALS-associated SOD1-mutant A4V Open
The accumulation of toxic protein aggregates is thought to play a key role in a range of degenerative pathologies, but it remains unclear why aggregation of polypeptides into non-native assemblies is toxic and why cellular clearance pathwa…
View article: Assessing computational predictions of the phenotypic effect of cystathionine‐beta‐synthase variants
Assessing computational predictions of the phenotypic effect of cystathionine‐beta‐synthase variants Open
Accurate prediction of the impact of genomic variation on phenotype is a major goal of computational biology and an important contributor to personalized medicine. Computational predictions can lead to a better understanding of the mechani…
View article: Loss of DPP6 in neurodegenerative dementia: a genetic player in the dysfunction of neuronal excitability
Loss of DPP6 in neurodegenerative dementia: a genetic player in the dysfunction of neuronal excitability Open
Emerging evidence suggested a converging mechanism in neurodegenerative brain diseases (NBD) involving early neuronal network dysfunctions and alterations in the homeostasis of neuronal firing as culprits of neurodegeneration. In this stud…
View article: AmyPro: a database of proteins with validated amyloidogenic regions
AmyPro: a database of proteins with validated amyloidogenic regions Open
Soluble functional proteins may transform into insoluble amyloid fibrils that deposit in a variety of tissues. Amyloid formation is a hallmark of age-related degenerative disorders. Perhaps surprisingly, amyloid fibrils can also be benefic…
View article: Nuclear inclusion bodies of mutant and wild‐type p53 in cancer: a hallmark of p53 inactivation and proteostasis remodelling by p53 aggregation
Nuclear inclusion bodies of mutant and wild‐type p53 in cancer: a hallmark of p53 inactivation and proteostasis remodelling by p53 aggregation Open
Although p53 protein aggregates have been observed in cancer cell lines and tumour tissue, their impact in cancer remains largely unknown. Here, we extensively screened for p53 aggregation phenotypes in tumour biopsies, and identified nucl…
View article: Solubis: a webserver to reduce protein aggregation through mutation
Solubis: a webserver to reduce protein aggregation through mutation Open
Protein aggregation is a major factor limiting the biotechnological and therapeutic application of many proteins, including enzymes and monoclonal antibodies. The molecular principles underlying aggregation are by now sufficiently understo…