Genetic Neurodegenerative Diseases

Correction of RBFOX1 deficit rescues Huntington's disease mis-splicing and pathology

This study shows that increasing RBFOX1 levels in HD mice corrects mis-splicing and reduces neuropathology and motor symptoms.

Spinal cord phosphoproteome of a SCA2/ALS13 mouse model reveals alteration of ATXN2-N-term SH3-actin interactome and of autophagy via WNK1-MYO6-OPTN-SQSTM1

The paper analyzes the phosphoproteome and interactome of a SCA2/ALS13 mouse model to identify altered signaling and protein interactions linked to neurodegeneration.

Parallel in-depth analysis of repeat expansions: an updated Clin-CATS workflow for nanopore R10 flow cells

The paper updates the Clin-CATS workflow to analyze repeat expansions using Oxford Nanopore R10 flow cells, expanding gene panels and improving detection of complex repeats.

Association of cerebellar inflammation and neurodegeneration in a novel spinocerebellar ataxia type 13 mouse model

This study creates a novel SCA13 mouse model with a R424H mutation, showing motor deficits, Purkinje cell loss, cerebellar inflammation, and atrophy, linking neuroinflammation to neurodegeneration.

A Novel Early Onset Spinocerebellar Ataxia 13 BAC Mouse Model with Cerebellar Hypoplasia, Tremor, and Ataxic Gait

This paper presents a novel BAC mouse model of SCA13 with cerebellar hypoplasia, tremor, and ataxic gait, mimicking human disease features.

Huntington's disease phenocopy syndromes revisited: a clinical comparison and next-generation sequencing exploration

This study estimates the prevalence of HD phenocopy syndromes, finds clinical distinctions are difficult, and uses whole-genome sequencing to identify one ATXN1 expansion in a subcohort.

Mapping the glial transcriptome in Huntington's disease using snRNAseq: Selective disruption of glial signatures across brain regions

This study uses snRNAseq to analyze glial cell heterogeneity in Huntington's disease across brain regions, identifying subtype-specific changes and potential mechanisms of glial dysfunction.

Identification and copy number variant analysis of enhancer regions of genes causing spinocerebellar ataxia

The paper identifies enhancer regions of SCA genes in human cerebellum and screens for copy number variants in undiagnosed patients, finding one potential CNV of unknown significance.

Enhanced Hippocampal Spare Capacity in Q175DN Mice Despite Elevated mHTT Aggregation

This study compares mHTT aggregation and neuropathology in the striatum and hippocampus of two HD mouse models, finding enhanced spare capacity in the hippocampus despite similar mHTT levels.

CCG interruptions are unstable and hypermethylated in DM1 patients

This study shows CCG interruptions in DM1 are unstable and hypermethylated, contributing to CTG repeat stabilization.

Stick-slip unfolding favors self-association of expanded HTT mRNA

The paper investigates the folding behavior of expanded HTT mRNA and finds that stick-slip dynamics contribute to its aggregation propensity.

Somatic instability of the FGF14-SCA27B GAA·TTC repeat reveals a marked expansion bias in the cerebellum

This study examines somatic instability of the FGF14 GAA·TTC repeat in SCA27B, finding a cerebellar-specific expansion bias and increased instability in cerebellar regions compared to other brain areas.

Fragile polyQ assemblies cause Golgipathy in Huntington's disease

This study identifies polyQ assemblies in HD cells as dynamic structures that regulate Golgi function, showing that mutant HTT disrupts their stability and leads to Golgipathy.

Increased frequency of repeat expansion mutations across different populations

The paper estimates the frequency of repeat expansion mutations across populations using whole genome sequencing data and finds higher expected prevalence than current reports.

Purkinje Cell-specific Deficiency in SEL1L-HRD1 Endoplasmic Reticulum-Associated Degradation Causes Progressive Cerebellar Ataxia in Mice

This study shows that SEL1L-HRD1 ERAD is essential for Purkinje cell function and causes progressive cerebellar ataxia in mice.

DRED: A Comprehensive Database of Genes Related to Repeat Expansion Diseases

DRED is a manually-curated database of 61 known and 516 predicted genes related to repeat expansion diseases, providing repeat information and links to external resources.

Interaction between histone residue H3K56 and mismatch repair protein MutSβ drives CAG repeat expansion

The paper shows that H3K56 interacts with MutSβ to recruit it to chromatin, promoting CAG repeat expansion, and suggests targeting this interaction to prevent neurodegenerative disorders.

Poly ADP-Ribose Signaling is Dysregulated in Huntington Disease Patients

The paper identifies a deficient PAR response in Huntington disease patients, suggesting a potential therapeutic target for early intervention.

Early Neurodevelopmental Defects in Huntingtons Disease are Driven by Choroid Plexus Overgrowth and Altered Paracrine Signaling

This study identifies early neurodevelopmental defects in juvenile-onset HD driven by choroid plexus overgrowth and altered paracrine signaling using organoid and mouse models.

Deciphering the ferroptosis pathways in dorsal root ganglia of Friedreich ataxia models. The role of LKB1/AMPK, KEAP1, and GSK3beta in the impairment of the NRF2 response

This study investigates ferroptosis pathways in Friedreich ataxia models, showing frataxin deficiency disrupts NRF2 activation and leads to oxidative stress and ferroptosis in DRG neurons.

AAGGG repeat expansions trigger RFC1-independent synaptic dysregulation in human CANVAS Neurons

This study shows that AAGGG repeat expansions cause synaptic defects in CANVAS neurons independently of RFC1, with phenotypes corrected by repeat deletion.

Advancing molecular, phenotypic and mechanistic insights of FGF14 pathogenic expansions (SCA27B)

This study identifies the complete sequences of pathogenic and non-pathogenic FGF14 repeat expansions in patients with cerebellar ataxia, revealing a lower pathogenic threshold and providing mechanistic insights into disease causation.

Preclinical evaluation of the novel CHDI-650 PET ligand for non-invasive quantification of mutant huntingtin aggregates in Huntington's disease

This paper evaluates [18F]CHDI-650, a novel PET radiotracer, for imaging mutant huntingtin aggregates in HD mouse models, showing genotype discrimination at 3 and 9 months.

Mutant Huntingtin impairs neurodevelopment in human brain organoids through CHCHD2-mediated neurometabolic failure

This study shows that mutant Huntingtin causes neurodevelopmental issues in human brain organoids by disrupting CHCHD2, leading to mitochondrial and metabolic problems.

NMR structures and magnetic force spectroscopy studies of small molecules binding to models of an RNA CAG repeat expansion

This paper reports NMR structures and magnetic force spectroscopy studies of small molecules binding to RNA CAG repeat expansions, revealing their binding modes and structural effects.

CAG repeat-selective compounds reduce abundance of expanded CAG RNAs in patient cell and murine models of SCAs

The paper identifies small molecules that reduce expanded CAG RNA abundance in SCA patient and mouse models, showing repeat-selective effects across multiple SCAs.

A Novel Methodology to Recalibrate Pathogenic Range of SCA36 Repeat Expansions for PGT-M

This paper recalibrates the pathogenic range of SCA36 repeat expansions using Bayesian methods and long-read sequencing to improve clinical applicability for preimplantation genetic testing.

Global Huntingtin Knockout in Adult Mice Leads to Fatal Neurodegeneration that Spares the Pancreas

This study shows that global Htt knockout in adult mice causes neurodegeneration and subcortical calcification but not pancreatitis, and increases neurofilament light chain levels.

mRNA nuclear clustering leads to a difference in mutant huntingtin mRNA and protein silencing by siRNAs in vivo

The paper shows that di-valent siRNA reduces wild-type Htt mRNA but not mutant HTT mRNA in HD mouse models, with mutant transcripts remaining clustered in the nucleus.

Blocking the ability of huntingtin to bind membranes: a therapeutic strategy for Huntingtons disease

This study evaluates blocking huntingtin membrane binding as a therapeutic strategy for HD, identifying two compounds that alleviate HD phenotypes in C. elegans.