Canadian Association for Neuroscience

Loss of TDP-43 function contributes to neurodegeneration. Using CRISPRi screening in human neurons, Ye et al. identify DCPS as a modifier of TDP-43 loss-of-function-mediated toxicity. Reducing DCPS restores RNA turnover, rescues transcriptomic dysregulation via P-body regulation, and improves neuronal survival, revealing a potential therapeutic target for ALS/FTD.

The FLEXITau platform provides detailed, quantitative, peptide-resolved molecular maps of tau for six tauopathies, as well as symptomatic and asymptomatic controls. The data identify disease-specific molecular signatures using machine learning, enabling accurate classification of tauopathies and providing critical targets for diagnostic and therapeutic development.

CRISPR screens in iPSC-derived neurons reveal that the E3 ubiquitin ligase CRL5SOCS4 ubiquitinates tau, that CUL5 expression is correlated with resilience in human Alzheimer’s disease, and that electron transport chain dysfunction alters tau degradation by the proteasome.

This study describes the cell-type-specific lysosomal proteome across the major brain cell types and identifies SLC45A1 as a neuron-specific lysosomal sugar exporter linked to lysosomal storage disease.

Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

TDP-43 is an RNA and DNA binding protein that plays major roles in regulating RNA processing. In particular, TDP-43 dysfunction leads to the accumulation of cryptic splice isoforms that result from im...

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are overwhelmingly linked to TDP-43 dysfunction. Mutations in TDP-43 are rare, indicating that the progressive accumulation of exo...