Genetic Neurodegenerative Diseases

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

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

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.

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

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.

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

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.

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

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

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.

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

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

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.

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.

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

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

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.

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

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.

This study shows that HTT polyQ expansions disrupt motor and adaptor recruitment to vesicles, causing transport defects and altered responses to neuroinflammatory stress.

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.

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

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

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

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

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

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

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.

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.