Genetic Neurodegenerative Diseases

Huntingtin interactome reveals huntingtin role in regulation of double strand break DNA damage response (DSB/DDR), chromatin remodeling and RNA processing pathways

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 AAV-CRISPR at different ages enables sustained amelioration of Huntington's disease deficits in BAC226Q mice

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

Impaired motor activity in a CRISPR SCA5 L253P knock-in mouse is associated with selective beta-III-spectrin subcellular redistribution in the cerebellum

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.

A neural basis for mutant ATAXIN-1 induced respiratory dysfunction in mouse models of Spinocerebellar ataxia type 1

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

Scn4b Modulates Huntington's Disease Phenotype Severity in vivo

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

Zebrafish knockout models of atxn1a, atxn1b, and atxn1l reveal distinct and shared phenotypic and transcriptomic alterations

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

Novel monoclonal antibodies against the C-terminal HEAT domain of Huntingtin

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.

Loss of interruption in the HTT CAG repeat is associated with increased somatic expansion and loss of medium spiny neurons in HD

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.

Large-scale Perturbation of Systems Biology-Derived Genes Reveals Modifiers of HD-associated Transcriptomic Networks and Pathology

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

Huntington's disease LIG1 modifier variant increases ligase fidelity and suppresses somatic CAG repeat expansion

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.

Investigation of autophagy-activating molecules in a glia-specific Spinocerebellar ataxia type 1 model

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.

The Hsp40 co-chaperone DNAJC7 regulates polyglutamine aggregation and exhibits context-dependent effects on polyglycine aggregation

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.

A novel uN2CpolyG Transgenic Mouse Model Recapitulates Multisystemic polyG Proteinopathy Pathology of Neuronal Intranuclear Inclusion Disease

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

High-throughput quantification of huntingtin mRNA expression and aggregation in mouse brain using automated RNAscope imaging.

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.

FibrilPaints for visualisation and ubiquitination of Huntingtin amyloid fibrils

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

Patient-derived 3D engineered human muscle model recapitulates CLCN1 mis-splicing and myotonia in myotonic dystrophy type 1

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

Allele-specific expression of ATXN3 in blood samples of Machado-Joseph disease expansion carriers.

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.

Mechanism of ATXN8OS CTA/CTG repeat-associated non-AUG translation revealed by approaches ranging from cell-free translation to live-cell imaging.

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.

Blood glucose homeostasis in patients with mild to moderate Spinocerebellar Ataxia type 2

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

Understanding corticosterone fluctuations and HPA-axis regulation in a mouse model of Spinocerebellar ataxia type 3

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

GFP-Free Live-Neuron Quantitative Imaging Reveals Compartmentalization and Growth Dynamics of PolyQ Aggregates

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

In Vivo Expression of an SCA27A-linked FGF14 Mutation Results in Haploinsufficiency and Impaired Firing of Cerebellar Purkinje Neurons

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

Cardiorenal and hepatic dysfunctions underlie metabolic alterations in the spinocerebellar ataxia type 7 mice

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

Ketosis rescues frataxin deficiency and corrects disease phenotypes in an FRDA animal model

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

Modeling Huntington disease against age-related genes reveals CXXC4 as an epigenetic target to restore DRD1 striatal neuron activity

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

F2,6BP restores mitochondrial genome integrity in Huntingtons Disease

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

Enhanced mGluR1 function causes motor deficits and region-specific Purkinje cell dysfunction

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

Zebrin molecular identity and cerebellar location determine Purkinje cell vulnerability in Christianson syndrome mice

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.

Enhancing the detection of HTT1a with neoepitope antibodies in mouse models of Huntington's disease

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.

Quercetin selectively reduces expanded repeat RNA levels in models of myotonic dystrophy

Quercetin reduces toxic RNA levels and rescues MBNL-dependent mis-splicing in DM1 and DM2 models.