Amyotrophic Lateral Sclerosis Research

The paper identifies non-linear gene sets from blood cells to classify ALS with high accuracy using machine learning and validates findings in lab samples and iPSC-derived motor neurons.

Skeletal muscle from individuals at elevated genetic risk for ALS/FTD undergoes progressive metabolic reprogramming far before disease onset.

This study shows that elevated TAF15 expression in neurons causes oxidative stress, neurotoxicity, and FTD-like behaviors, which can be reversed by antioxidants.

This study shows methionine oxidation in TDP-43's C-terminal domain disrupts structure and phase separation through region-specific mechanisms.

This paper shows that ALS/FTD-linked TDP-43 mutations cause DNA breaks in genes controlling excitatory neurotransmission by impairing topoisomerase IIβ function.

This study develops a gene therapy strategy using snRNAs to correct mis-splicing of STMN2 and UNC13A in TDP-43 proteinopathies, showing restoration of protein levels and axonal regeneration in motor neurons.

This study shows that PGRN loss in human cerebral organoids causes mitochondrial dysfunction and ferroptosis through oxidative stress and iron accumulation.

This study shows that mutant FUS reduces ALKBH5 expression, increasing m6A levels, and that restoring m6A alleviates ALS pathology in Drosophila models.

The paper develops U7 snRNA therapeutics to correct TDP-43-dependent mis-splicing in ALS, restoring gene expression and neuronal function in human iPSC-derived neurons.

This paper identifies CSPG4 as a mediator of arginine-rich DPR uptake and cell-to-cell transmission, suggesting it as a therapeutic target for ALS/FTD.

This study identifies how ataxin-2 reduction promotes neuroprotection by activating metabolic programs in neurons and astrocytes, enhancing energy production and trophic support.

The paper identifies cryptic splicing events (CEs) sensitive to TDP-43 loss and develops a composite score to detect TDP-43 pathology across tissues.

This study identifies ATP8A2 as a TDP-43 target whose loss leads to PS exposure and neuroinflammation, suggesting immune cell inhibition as a therapeutic strategy for ALS-FTD and CAMRQ4.

The paper evaluates 23 commercial antibodies for detecting FET proteins, identifies specific ones, and provides a validated panel for reliable research.

This study shows that mislocalisation of TDP-43 to the cytoplasm in neurons or oligodendrocytes causes axonopathy and dysmyelination, highlighting the role of cell-type-specific loss of function in neurodegeneration.

This study shows nuclear-import receptors suppress RNA-binding protein phase transitions by remodeling the dilute phase, preventing disease-linked aggregation.

This study identifies vitamin D3 as a potential inhibitor of TDP-43's mitochondrial mis-localization through molecular docking and simulation of the M3 region.

The paper generates isogenic iPSC lines with a C9ORF72 G4C2 repeat expansion to model ALS and FTD, showing both loss- and gain-of-function pathologies.

This study shows that export-biased TDP-43 with intact 3' UTR leads to cytoplasmic aggregation and splicing defects, even when exogenous levels match endogenous, suggesting loss of nuclear function.

This study investigates the phase behavior of TDP-43 and hnRNP H1, revealing an aggregate-to-droplet transition and domain matching in phase separation of LCD-containing proteins.

The paper investigates TDP-43 SUMOylation and its role in DNA damage repair under oxidative stress.

Human brain organoids show that a TDP-43 mutation causes RNA mis-splicing and neuronal stress in ALS.

This study shows KIF5A binds RNA to regulate synaptic mRNA localization and stress granules, with ALS mutations disrupting synaptic homeostasis.

This study overexpresses TDP-43 in rhesus macaques to create an ALS model, showing motor neuron degeneration and widespread TDP-43 pathology.

The paper shows that loss of FXR1 and FXR2 leads to TDP-43 accumulation in stress granules, linking FXP family reduction to neurodegenerative pathology.

This study shows that TDP-43 dysfunction impairs proteostasis and worsens neurological outcomes after brain injury in mice.

The paper develops an MRI-based machine learning classifier to identify presymptomatic C9orf72 carriers at high risk of disease onset within two years.

This study uses intramuscular AAV therapy to silence SOD1 in neonatal mice, delaying ALS onset and improving survival and motor function.

This study evaluates a gene therapy for SOD1-ALS, showing improved survival and CNS inflammation in treated mice with dose-dependent hSOD1 reduction.

The paper identifies BAG6 as a suppressor of UBQLN2 misfolding in ALS-dementia by analyzing interactome changes in mutant UBQLN2 proteins.