Skip to main content

Aggregator

Disentangling associations between complex traits and cell types with seismic

1 year 1 month ago
Integrating single-cell RNA sequencing with Genome-Wide Association Studies (GWAS) can uncover cell types involved in complex traits and disease. However, current methods often lack scalability, interpretability, and robustness. We present seismic, a framework that computes a novel specificity score capturing both expression magnitude and consistency across cell types and introduces influential gene analysis, an approach to identify genes driving each cell type-trait association. Across over...
Qiliang Lai

Synthetic chaperone based on Hsp90-Tau interaction inhibits Tau aggregation and rescues physiological Tau-Microtubule interaction

1 year 1 month ago
The accumulation of intracellular aggregates of Tau protein is one main hallmark of Alzheimer's disease (AD) and is the consequence of Tau conformational changes, increased phosphorylation, and self-association to form fibrillar aggregates. This pathological process prevents the physiological interaction of Tau with microtubules to the detriment of the structural integrity of neurons. In healthy cells, aberrant protein misfolding and aggregation are counteracted by chaperone proteins whose...
Davide Di Lorenzo

Parkinson disease is a fatty acidopathy

1 year 1 month ago
On the basis of extensive mechanistic research over three decades, Parkinson disease (PD) and related synucleinopathies have been proposed to be combined proteinopathies and lipidopathies. Evidence strongly supports a physiological and pathogenic interplay between the disease-associated protein α-synuclein and lipids, with a demonstrable role for lipids in modulating PD phenotypes in the brain. Here, we refine this hypothesis by proposing PD to be a disease specifically involving metabolic...
Saranna Fanning

Large-scale visualization of alpha-synuclein oligomers in Parkinson's disease brain tissue

1 year 1 month ago
Parkinson's disease (PD) is a neurodegenerative condition characterized by the presence of intraneuronal aggregates containing fibrillar ɑ-synuclein known as Lewy bodies. These large end-stage species are formed by smaller soluble protein nanoscale assemblies, often termed oligomers, which are proposed as early drivers of pathogenesis. Until now, this hypothesis has remained controversial, at least in part because it has not been possible to directly visualize nanoscale assemblies in human brain...
Rebecca Andrews

Targeted clearance of extracellular Tau using aptamer-armed monocytes alleviates neuroinflammation in mice with Alzheimer's disease

1 year 1 month ago
Extracellular Tau determines the progression of Alzheimer's disease, yet therapeutic strategies targeting it are hindered by poor brain delivery and limited clearance. Here we developed a Tau-clearing cell therapy based on monocytes functionalized with a high-affinity Tau-specific aptamer. The aptamer was covalently conjugated to the surface of monocytes (derived from bone marrow leucocytes and cultured under monocyte-inducing conditions) via bioorthogonal chemistry without affecting their...
Yuting Zhuo