Header

Search

Seeded TDP-43 Aggregation Model Developed at DQBM Reveals Early Neurodegenerative Signatures

Researchers at the DQBM) led by Prof. Magdalini Polymenidou, have developed a robust new model to study the pathology of the RNA-binding protein TDP-43, a major player in neurodegenerative diseases like ALS and frontotemporal dementia (FTD). The model demonstrates how TDP-43 aggregates—either from recombinant sources or patient brain tissue—spread between cells and lead to its functional loss, mimicking disease mechanisms. Using advanced imaging, RNA sequencing, and proteomics, the team uncovered early molecular signatures of TDP-43 dysfunction, offering a powerful platform for screening genetic and pharmacological modifiers. This innovative work strengthens DQBM’s focus on translational neuroscience and opens new avenues for therapeutic discovery.

Reference:
Scialò et al., Neuron (2025), https://doi.org/10.1016/j.neuron.2025.03.008.

TDP-43 pathology characterizes neurodegenerative diseases. Scialo ` et al. use in vitro-generated and patientderived TDP-43 aggregates as seeds to show that seed-induced TDP-43 cytoplasmic aggregation causes its loss of function and downstream RNA misregulation. This new cell model shows TDP-43 aggregation and loss of function without overexpression or knockdown.
Graphical Abstract

Unterseiten