Albert R. La Spada

PQBP1-dependent alternative RNA splicing underlies high calorie diet-induced cognitive impairment

This study identifies PQBP1-dependent alternative RNA splicing as a mechanism underlying HFD-induced cognitive impairment through effects on synaptic vesicle release.

Characterization of the frameshift c.515dupC knock-in mouse model of HSPB8-associated myopathy (MFM13) and evaluation of Trehalose as autophagy modulating therapy.

This study characterizes a HSPB8 knock-in mouse model of MFM13 and evaluates trehalose as a potential autophagy modulating therapy for HSPB8-related myopathy.

Multimodal analysis of cell-free DNA identifies epigenetic biomarkers for amyotrophic lateral sclerosis diagnosis and progression

This study identifies epigenetic biomarkers in cell-free DNA for ALS diagnosis and progression prediction using methylation analysis.

PPARδ activation in microglia drives a transcriptional response that primes phagocytic function while countering inflammatory activation

This study shows PPARδ activation in microglia reduces inflammation and enhances phagocytic function, shifting microglia toward a disease-associated state in neurodegenerative models.

An optimized variant prioritization process for rare disease diagnostics: recommendations for Exomiser and Genomiser

This paper optimizes variant prioritization parameters for Exomiser and Genomiser to improve diagnostic yield in rare disease cases using WES and WGS data.

Huntingtin preserves mitochondrial genome integrity in neurons, which is impaired in Huntingtons disease

The paper shows that Huntingtin (HTT) helps maintain mitochondrial DNA integrity by organizing a repair complex, which is disrupted by mutant HTT in Huntington's disease, leading to DNA damage and motor deficits in a fly model.

TDP-43 dysregulation of polyadenylation site selection is a defining feature of RNA misprocessing in ALS/FTD and related disorders

The paper identifies TDP-43 dysregulation of polyadenylation site selection as a key feature of RNA misprocessing in ALS/FTD and related disorders, linking it to increased tau phosphorylation.

Skeletal Muscle TFEB Signaling Promotes Central Nervous System Function and Reduces Neuroinflammation during Aging and Neurodegenerative Disease

This study shows that enhancing skeletal muscle TFEB signaling reduces neuroinflammation and tau pathology in aging and neurodegenerative disease models.

PD-linked LRRK2 G2019S mutation impairs astrocyte morphology and synapse maintenance via ERM hyperphosphorylation

This study shows that the LRRK2 G2019S mutation impairs astrocyte morphology and synapse maintenance by hyperphosphorylating ERM proteins, which disrupts the Ezrin/Atg7 interaction and autophagy.

Purkinje-Enriched snRNA-seq in SCA7 Cerebellum Reveals Zebrin Identity Loss as a Central Feature of Polyglutamine Ataxias

The paper uses snRNA-seq to study Purkinje cells in SCA7 mice, revealing zebrin-II subtype loss as a key feature of polyglutamine ataxias.

Antagonistic roles of canonical and alternative RPA in tandem CAG repeat diseases

The paper investigates the roles of canonical and alternative RPA in CAG repeat diseases, finding that Alt-RPA antagonizes RPA's suppression of CAG expansions, contributing to disease pathogenesis.