Genetic Neurodegenerative Diseases

Modulation of huntingtin S421 phosphorylation in a Huntington's disease mouse model and its detection in nonhuman primate cerebrospinal fluid

The paper develops an ultrasensitive immunoassay to detect S421 phosphorylation of huntingtin in HD models and nonhuman primate CSF, linking it to disease progression and identifying PRKACA as a kinase involved.

Huntingtin loss-of-function contributes to transcriptional deregulation in Huntington's disease

This study identifies transcriptional deregulation in Huntington's disease by comparing HD and HTT-knockout cells, showing that loss of HTT function drives early transcriptional changes.

Blocking somatic repeat expansion and lowering huntingtin via RNA interference synergize to prevent Huntingtons disease pathogenesis in mice

This study shows that combining RNAi to silence MSH3 and HTT reduces huntingtin inclusions and restores gene expression in HD mice.

Dysregulated synaptic gene expression in oligodendrocytes of spinal and bulbar muscular atrophy

This study identifies dysregulated synaptic gene expression in oligodendrocytes of SBMA mice, highlighting early cell-to-cell communication changes as a potential therapeutic target.

Dysregulated MEG3 in Myotonic Dystrophy 1: nuclear retention, pathological role, and therapeutic correction by antisense conjugates.

This study shows MEG3 is upregulated in DM1 and exhibits nuclear retention, with antisense conjugates correcting MEG3 levels in mice.

Characterisation of DMPK and MBNL1 expression in cell models of Myotonic Dystrophy: A platform for drug screening

This paper develops a cell-based platform to quantify DMPK and MBNL1 in DM1 models and evaluates therapeutic strategies targeting DMPK.

Chemical targeting of the ATXN1 aa99-163 interaction site suppresses polyQ-expanded protein dimerization

The paper identifies an interaction site between ATXN1 and MED15 and shows that targeting this site with a chemical compound reduces polyQ-expanded protein dimerization in SCA1.

Direct observation of secondary nucleation in huntingtin amyloid formation by High-Speed Atomic Force Microscopy

This study uses high-speed atomic force microscopy to directly observe secondary nucleation in huntingtin amyloid formation, revealing dynamic processes and the role of flanking segments.

Lowering the HTT1a transcript as an effective therapy for Huntingtons disease

The paper shows that lowering HTT1a transcript levels delays molecular and neuropathological phenotypes in a Huntington's disease mouse model.

Treating Myotonic Dystrophy with artificial RNA endonucleases to specifically degrade toxic RNA expansions

This paper develops artificial RNA endonucleases (ARCs) that specifically degrade toxic RNA expansions in DM1, showing efficacy in cells and mouse models with low immunogenicity and off-target effects.

Molecular consequences of SCA5 mutations in the spectrin-repeat domains of beta-III-spectrin

This study investigates how SCA5 mutations in the spectrin-repeat domains of beta-III-spectrin affect interactions with alpha-II-spectrin and actin.

The Insertion of an ATTTC Repeat in an Alu Element Hyperactivates a Primate-Specific Neurodevelopmental Enhancer in Spinocerebellar Ataxia Type 37

The paper shows that an ATTTC repeat insertion in an Alu element enhances a DAB1 enhancer, leading to neuronal dysfunction in SCA37.

Double strand breaks drive toxicity in Huntington's disease mice with or without somatic expansion.

This study shows that double strand breaks (DSBs) independently drive Huntington's disease toxicity in mice, separate from somatic expansion, and that inhibiting DSBs can reverse neuronal toxicity.

Epigenetic mechanisms governing cell type specific somatic expansion and toxicity in Huntington's disease

This study identifies epigenetic mechanisms linking cell type-specific enhancer activity to somatic CAG expansion and toxicity in Huntington's disease.

Polyglutamine expansion induced dynamic misfolding of Androgen Receptor

This study uses computational modeling to show that polyglutamine expansion in the androgen receptor's N-terminal domain causes dynamic misfolding, altering interdomain interactions and potentially leading to SBMA pathology.

MSH3 is a genetic modifier of somatic repeat instability in X-linked dystonia parkinsonism

This study identifies MSH3 as a genetic modifier of CCCTCT repeat instability in XDP, showing its impact on both expansion and contraction in blood and brain tissues.

A FAN1 point mutation associated with accelerated Huntington's disease progression alters its PCNA-mediated assembly on DNA

This study identifies a FAN1 mutation linked to faster Huntington's disease progression and shows it disrupts PCNA-mediated FAN1 assembly on DNA.

Complex associations of genetic/epigenetic variations of CGG repeats with patient phenotypes in oculopharyngodistal myopathy

The paper investigates how genetic and epigenetic variations in CGG repeats affect OPDM patient phenotypes, finding complex relationships between repeat size, sequence context, and methylation.

Huntingtin inclusion bodies have distinct immunophenotypes and ubiquitination profiles in the Huntington's disease human cerebral cortex

This study examines the immunophenotypic and ubiquitination diversity of Huntingtin inclusion bodies in Huntington's disease cerebral cortex, revealing heterogeneity in composition and degradation pathways.

Mitochondrial dysfunction in Machado Joseph disease: insights from a multi-model system

This study investigates mitochondrial dysfunction in Machado Joseph disease using multiple models, finding impaired oxidative phosphorylation and altered mitochondrial morphology in mice and zebrafish.

Transient interdomain interactions modulate the monomeric structural ensemble and self-assembly of Huntingtin Exon 1

This study uses molecular dynamics simulations to show that transient interdomain interactions in Httex1 modulate its structural ensemble and self-assembly, contributing to aggregation in Huntington's disease.

Interventionally targeting somatic CAG expansions can be a rapid disease-modifying therapeutic avenue: Preclinical evidence.

This study shows that reducing somatic CAG expansions in HD mice improves motor function and disease markers, suggesting therapeutic potential for HD and similar repeat expansion diseases.

Mesoscale Imaging of Cortical Sensorimotor Integration in Huntington's Disease Mice During Reward-Guided Behaviour

This study uses mesoscale calcium imaging in HD mice during a sensory-guided task to explore altered cortical activity and its behavioral implications.

Challenges and advances for huntingtin detection in cerebrospinal fluid: in support of relative quantification

This study investigates challenges in mHTT quantification in CSF, showing that absolute quantitation is unreliable due to protein complexity and recommends relative quantitation instead.

Intersecting impact of CAG repeat and Huntingtin knockout in stem cell-derived cortical neurons

This study compares the effects of HTT knockout and CAG repeat expansion in cortical neurons, identifying shared and distinct biological pathways involved in HD.

Multiomics approach identifies SERPINB1 as candidate progression biomarker for Spinocerebellar Ataxia type 2

The paper identifies SERPINB1 as a potential biomarker for SCA2 progression through multi-omics analysis in mice and validation in human patients.

Anti-gene oligonucleotides targeting Friedreichs ataxia expanded GAA:TTC repeats increase Frataxin expression

This study shows that anti-gene oligonucleotides targeting GAA*TTC repeats in Friedreichs ataxia increase FXN expression in patient cells.

Utilization of CoRDS Registry to Monitor Quality of Life in Patients with VCP Multisystem Proteinopathy

This study uses the CoRDS registry to track quality of life in VCP disease patients, finding significant declines in mobility and function over time.

ATXN2L primarily interacts with NUFIP2, the absence of ATXN2L results in NUFIP2 depletion, and the ATXN2-polyQ expansion triggers NUFIP2 accumulation

This study identifies ATXN2L interactors and shows that its absence leads to NUFIP2 depletion, while ATXN2-polyQ expansion causes NUFIP2 accumulation.

Altered Huntingtin-Chromatin Interactions Predict Transcriptional and Epigenetic Changes in Huntington's Disease Mouse Models

The paper identifies altered huntingtin-chromatin interactions in HD mouse models, linking them to transcriptional and epigenetic changes in striatal tissue.