Publications by authors named "T M Serdiuk"
Mutations in GBA1 encoding the lysosomal enzyme β-glucocerebrosidase (GCase) are among the most prevalent genetic susceptibility factors for Parkinson's disease (PD), with 10-30% of carriers developing the disease. To identify genetic modifiers contributing to the incomplete penetrance, we examined the effect of 1634 human transcription factors (TFs) on GCase activity in lysates of an engineered human glioblastoma line homozygous for the pathogenic GBA1 L444P variant. Using an arrayed CRISPR activation library, we uncovered 11 TFs as regulators of GCase activity.
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- The study investigates the structures of α-synuclein fibrils linked to neurodegenerative disorders, revealing how variations in pH and buffer conditions impact the selection of different fibril polymorphs.
- The researchers found that within the physiological pH range, polymorph selection is influenced by secondary nucleation mechanisms, even when seeds are present.
- Additionally, two new polymorphs were identified, highlighting the importance of environmental factors like pH in understanding amyloid aggregation and its implications for disease-relevant research.
Extracellularly released molecular inflammasome assemblies -ASC specks- cross-seed Aβ amyloid in Alzheimer's disease. Here we show that ASC governs the extent of inflammation-induced amyloid A (AA) amyloidosis, a systemic disease caused by the aggregation and peripheral deposition of the acute-phase reactant serum amyloid A (SAA) in chronic inflammatory conditions. Using super-resolution microscopy, we found that ASC colocalized tightly with SAA in human AA amyloidosis.
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- The study reveals how the physical interactome of proteins can change in response to structural alterations, which affects cell behavior and relates to diseases like Parkinson’s.
- Researchers utilized limited proteolysis-mass spectrometry (LiP-MS) to investigate structure-specific protein-protein interactions (PPIs), successfully identifying known and new interactors of the protein alpha-synuclein, a key player in Parkinson’s disease.
- The methodology demonstrated can be applied broadly to examine structure-specific interactomes of various proteins, regardless of their modifications or binding states, enhancing our understanding of disease mechanisms.
In cell membranes, G protein-coupled receptors (GPCRs) interact with cholesterol, which modulates their assembly, stability, and conformation. Previous studies have shown how cholesterol modulates the structural properties of GPCRs at ambient temperature. Here, we characterized the mechanical, kinetic, and energetic properties of the human β-adrenergic receptor (βAR) in the presence and absence of the cholesterol analog cholesteryl hemisuccinate (CHS) at room temperature (25°C), at physiological temperature (37°C), and at high temperature (42°C).
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