Genetic Neurodegenerative Diseases

Data-driven model reveals increased stability of CAG-expanded huntingtin RNA due to MID1 binding

The paper develops a computational model to show that MID1 binding increases mutant huntingtin RNA stability, validated experimentally.

Macrocyclic Peptide Tools for Huntingtin-bound HAP40

The paper develops macrocyclic peptides that target HAP40, enabling the study of HTT-HAP40 interactions and their role in Huntington's disease.

Striatal neuron excitability is regulated by huntingtin in the adult brain

This study shows that loss of wild-type huntingtin in adult striatal neurons reduces excitability and causes neuroinflammation without affecting tissue structure or motor behavior.

Temporal single-cell atlas of full-length Huntington's disease mouse model defines stage-specific signatures of corticostriatal dysfunction

The paper creates a temporal single-nucleus transcriptomic atlas of Huntington's disease mouse models to identify stage-specific transcriptional changes in corticostriatal regions.

Single-cell transcriptomics and mouse model phenotyping for biomarker screen of peripheral blood biomarkers in Huntington disease

The paper uses single-cell RNA-seq and mouse models to identify potential peripheral blood biomarkers for Huntington disease, finding Irf7 upregulation correlates with motor deficits.

Inhibition of the mitochondrial pyruvate carrier attenuates the integrated stress response activation in a cellular model of Huntington's disease

This study shows that inhibiting the mitochondrial pyruvate carrier modulates the integrated stress response differently in wild-type and mutant huntingtin-expressing cells.

Lipid Composition Controls the Huntingtin Exon1 Membrane-Association and Differentially Modulates its Flanking Regions Dynamics

This study examines how lipid composition affects Httex1 membrane association and the dynamics of its flanking regions, revealing distinct behavior between the N17 and PRR domains.

Intranuclear polyglycine aggregation drives neurodegeneration through epigenetic repression of chromatin accessibility and transcription

This study shows intranuclear polyG aggregates cause more severe neurodegeneration than cytoplasmic ones by repressing chromatin accessibility and transcription through epigenetic mechanisms.

HUNTINGTON DISEASE ALTERS THE PATTERNING OF NEOCORTICAL AREA IN MICE

This study shows that Huntington disease in mice causes early embryonic changes in neocortical patterning, leading to postnatal sensorimotor deficits.

C57BL/6 BAC-CAG Huntingtons disease mice show somatic CAG expansion and responses to small interfering RNAs comparable to the FVB strain

The paper compares somatic CAG expansion and siRNA responses in C57BL/6 and FVB BAC-CAG HD mouse models, finding comparable expansion and MSH3-targeted siRNA efficacy.

Huntingtin CAG repeat is a continuous modifier of brain structure and health vulnerability

This study shows that HTT CAG repeat length within the normal and intermediate range is associated with brain structure and neuropsychiatric risk, challenging the view of CAG repeats as purely categorical.

TRACE: Open-Source Software for Quantifying Somatic Variation of Tandem Repeats by Capillary Electrophoresis

TRACE is an open-source software that quantifies somatic instability of tandem repeats using capillary electrophoresis data, providing accessible tools for analyzing repeat expansion.

Glial-specific mitochondrial failure and redox imbalance drive regional vulnerability in Friedreich ataxia

This study identifies glial-specific mitochondrial failure and redox imbalance as drivers of regional vulnerability in Friedreich ataxia using a mouse model.

Genome-wide detection and clinical prioritization of tandem repeat outliers using long-read sequencing

The paper develops TRoLR, a pipeline using long-read sequencing to detect and prioritize pathogenic tandem repeat expansions in diverse populations, identifying known and novel expansions with clinical relevance.

TLR4-mediated neuroimmune signalling drives proprioceptive neuron degeneration in Friedreich ataxia

This study identifies TLR4-mediated neuroimmune signaling as a driver of proprioceptive neuron degeneration in Friedreich ataxia and shows that inhibiting TLR4 reduces disease progression.

Treatment of Huntington's disease with a pan-HTT-targeting CRISPR nuclease

This study develops a CRISPR-Cas9 system targeting all HTT alleles in HD mouse models, reducing mutant HTT and improving disease symptoms.

Establishment of spinocerebellar ataxia type 34 model mice accompanied by early glial activation and degeneration of cerebellar neurons

This study establishes a SCA34 mouse model with early glial activation and cerebellar neuron degeneration, linking microglial activation to motor dysfunction and neurodegeneration.

Duplication within 14q32.13 implicates a chimeric CLMN::SYNE3 RNA transcript in cerebellar ataxia

The paper identifies a chimeric CLMN::SYNE3 RNA transcript from a 14q32.13 duplication as the cause of SCA30, a form of cerebellar ataxia, through RNA-Seq and functional studies.

Pathogenic human huntingtin expression causes prolific intramuscular aggregation, leading to nuclear, metabolic, and physiological dysregulation in striated muscle.

This study shows that pathogenic huntingtin in Drosophila muscle causes protein aggregation, nuclear and mitochondrial dysfunction, and impaired neuromuscular performance without overt structural changes.

Distinct Cellular Effects of Myotonic Dystrophy type 2 RAN Tetrapeptides in Drosophila melanogaster

This study investigates the distinct toxic effects of QAGR and PACL peptides in Drosophila, showing they impair nucleolar function and autophagy or alter stress granule dynamics, contributing to DM2 pathogenesis.

Targeted 3'-end RNA sequencing uncovers cryptic polyadenylation in Huntington's disease linked to somatic instability and CAG repeat purity

This paper introduces 3TRS, a targeted RNA sequencing method to quantify HTT transcripts in HD models, revealing cryptic polyadenylation linked to somatic instability and CAG repeat purity.

Development of a novel VHH intrabody targeting the N17 region of huntingtin exon 1 protein that prevents inclusion body formation.

This paper develops a VHH intrabody that targets the N17 region of mHTT exon 1, reducing insoluble mHTT species and preventing inclusion body formation.

Neuronal cell line expressing full-length mutant huntingtin displays alteration of proteasome activity

The paper demonstrates that neuronal cells expressing mutant huntingtin show altered proteasome activity and aggregate formation.

IL-17A rescues motor deficits in a mouse model 1 of Spinocerebellar Ataxia Type 2

This study shows that IL-17A treatment improves motor function and Purkinje neuron activity in a mouse model of Spinocerebellar Ataxia Type 2.

A 5' UTR CCG expansion in TBC1D7 causes oculopharyngodistal myopathy

The paper identifies a CCG expansion in TBC1D7 as a cause of oculopharyngodistal myopathy, showing variable repeat structure and epigenetic regulation.

HAP40 functions as a proteostasis regulator by controlling huntingtin interactions and its release into the extracellular space

This study identifies HAP40 as a proteostasis regulator that controls HTT interactions and mHTT secretion, impacting cellular homeostasis and pathobiology.

Genetic or pharmacological disruption of the MSH3 Y245/K246 IDL binding pocket slows CAG repeat expansion

This study shows disrupting the MSH3 Y245/K246 DNA binding pocket reduces CAG repeat expansion in Huntington's disease models.

STRmie-HD enables interruption-aware HTT repeat genotyping and somatic mosaicism profiling across sequencing platforms

STRmie-HD is a tool for high-resolution genotyping of HTT repeat expansions and somatic mosaicism across sequencing platforms, capturing interruptions and rare variants with high sensitivity.

Friedreich ataxia transcriptomic dysregulation and identification of cell type-specific biomarkers: A systematic review and meta-analysis

This paper identifies cell-type-specific transcriptional biomarkers in Friedreich ataxia through meta-analysis of bulk RNA-seq datasets and develops an interactive transcriptomic atlas.

Vorinostat Rescues SQSTM1 Palmitoylation and Restores Dysfunctional Autophagy in Huntington Disease