Genetic Neurodegenerative Diseases

The paper identifies HTT interactors involved in DNA damage response, chromatin remodeling, and RNA processing pathways, revealing HTT's role in double strand break repair and its interaction with DNA-PKcs and RNA binding proteins.

Self-inactivating CRISPR targeting mutant huntingtin in HD mice achieved long-term rescue of neural pathology, motor deficits, weight loss and survival.

This paper develops a CRISPR knock-in mouse model of SCA5 L253P mutation, showing impaired motor activity and altered beta-III-spectrin localization in cerebellar Purkinje neurons.

This study identifies mutant ATAXIN-1's role in respiratory dysfunction in SCA1 mice by analyzing neural and skeletal muscle lineages.

This study shows that Scn4b modulates Huntington's disease severity by affecting gene expression and neuronal function in mouse models.

The paper generates zebrafish knockouts of atxn1a, atxn1b, and atxn1l to study their roles, finding distinct and shared developmental, behavioral, and transcriptomic effects.

The paper develops and validates novel monoclonal antibodies targeting the C-terminal HEAT domain of huntingtin, showing they detect full-length HTT regardless of polyglutamine length or HAP40 interaction.

The paper shows that loss of interruption in HTT CAG repeats increases somatic expansion and MSN loss in HD, with greater effects in patients with CAG-CCG LOI.

The paper uses genetic perturbations to identify modifiers of HD-associated transcriptomic networks and pathology in mice and patient-derived neurons.

This paper investigates the protective effect of the LIG1 K845N variant in Huntington's disease by showing it increases ligase fidelity and suppresses somatic CAG repeat expansion.

This study evaluates two autophagy activators in glia-specific SCA1 models, finding that AUTEN-99 improves survival and response times compared to AUTEN-67 and single-agent treatment.

This study develops cell-based models to evaluate genetic modifiers of polyQ and polyG aggregation, identifying DNAJC7 as a suppressor of polyQ aggregation but not polyG.

This study develops a transgenic mouse model that recapitulates the multisystemic pathology of neuronal intranuclear inclusion disease through polyG protein aggregates.

This study quantifies huntingtin mRNA expression and aggregation in mouse brains using a high-throughput RNAscope pipeline, revealing heterogeneity in mRNA accumulation and localization across brain regions.

This paper introduces FibrilPaint peptides that selectively bind and track HttEx1Q44 amyloid fibrils, enabling monitoring of fibril growth and molecular targeting through ubiquitination.

This paper develops a 3D human muscle model from DM1 patient myoblasts that recapitulates CLCN1 mis-splicing and myotonia, and tests therapeutic responses.

The paper investigates allele-specific expression of ATXN3 in blood samples of Machado-Joseph disease carriers, finding lineage-dependent allelic imbalance and its potential impact on age at onset.

This study identifies the mechanism of ATXN8OS CTA/CTG repeat-associated non-AUG translation through cell-free systems and live-cell imaging, revealing frameshifting and stress response involvement.

This study assesses blood glucose homeostasis in SCA2 patients and finds no major alterations but identifies correlations between glucose markers and disease severity.

This study examines HPA-axis regulation and corticosterone fluctuations in SCA3 mice, finding normal HPA-axis function and minimal stress impact on disease progression.

This study uses advanced imaging techniques to analyze polyQ aggregates in live neurons, revealing their growth dynamics and compartmentalization in Huntington's Disease.

This study shows that a mutation in FGF14 causes haploinsufficiency and impairs Purkinje neuron firing, leading to motor and cognitive deficits in mice.

This study identifies early systemic metabolic and organ dysfunction in SCA7 mice, highlighting peripheral contributions to disease pathogenesis.

This study shows that ketosis increases frataxin levels and improves disease symptoms in a Friedreich ataxia mouse model.

The paper identifies CXXC4 as an epigenetic target that can restore DRD1 striatal neuron activity in Huntington disease by leveraging age-related gene patterns.

This paper shows that F2,6BP restores mitochondrial genome integrity in Huntington's Disease by rescuing PNKP activity and mitochondrial function.

This study shows that enhanced mGluR1 function causes motor deficits and region-specific Purkinje cell dysfunction in a mouse model of SCA44.

This study shows that zebrin molecular identity and cerebellar location determine Purkinje cell vulnerability in Christianson syndrome mice, with anterior zebrin-negative cells dying earlier than posterior cells.

This study develops and evaluates two novel antibodies, 1B12 and 11G2, for more sensitive detection of HTT1a in Huntington's disease mouse models compared to the existing MW8 antibody.