Piera Pasinelli

Engineered Chimeric Proteins Functionally Replace ALS-causing Endogenous FUS and TDP-43 to Improve Neuronal Health

The paper engineers chimeric proteins to replace ALS-causing FUS and TDP-43, improving neuronal health by reducing aggregation and restoring nuclear functions.

A Human Neuronal Cell Model of Endogenous TDP-43 A315T Reveals Altered Protein Dynamics and Disease-Relevant Cellular Dysfunction

This study develops a human neuronal model with the TDP-43 A315T mutation to study ALS-related protein dysfunction and therapeutic responses.

Short RNA chaperones promote aggregation-resistant TDP-43 conformers to mitigate neurodegeneration

Short UG-rich RNAs bind and stabilize TDP-43 RNA-recognition motifs to allosterically destabilize its prion-like domain helical region, preventing aggregation and mitigating neurodegeneration in cells and mice.

A CAR-T Cell-Based Strategy for Eliminating Pathogenic Microglia in ALS

CAR-T cells targeting uPAR selectively ablate pathogenic microglia while sparing neurons, enabling precision immunotherapy for ALS.

Neuronal Activity-Dependent Gene Dysregulation in C9orf72 i3 Neuronal Models of ALS/FTD Pathogenesis

This study shows that C9orf72 repeat expansion neurons have altered transcriptomes under different stimulation conditions, revealing activity-dependent gene dysregulation in ALS/FTD.

Glucose Hypometabolism Prompts RAN Translation and Exacerbates C9orf72-related ALS/FTD Phenotypes

This study shows glucose hypometabolism in C9orf72-related ALS/FTD leads to DPR production, neuronal death, and motor dysfunction through GCN2 activation.

The nuclear import receptor Kapβ2 protein modifies neurotoxicity mediated by poly(GR) in C9orf72-linked ALS/FTD

This study shows that Kapβ2 protein interacts with poly(GR) and reduces its neurotoxicity in C9orf72-linked ALS/FTD by improving neuron survival.

C9orf72 poly(PR) mediated neurodegeneration is associated with nucleolar stress

This study shows that C9orf72 poly(PR) causes nucleolar stress and neurotoxicity, which can be mitigated by reducing p53 levels in fly and rat models.

EphrinB2 knockdown in cervical spinal cord preserves diaphragm innervation in a mutant SOD1 mouse model of ALS

This study shows that reducing ephrinB2 in spinal cord astrocytes of ALS mice preserves diaphragm innervation and respiratory function.

Astrocytic expression of ALS-causative mutant FUS leads to TNFa-dependent neurodegeneration in vivo

This study shows that astrocytic expression of mutant FUS causes TNF-dependent neurodegeneration in ALS, highlighting a therapeutic target.