Amyotrophic Lateral Sclerosis Research

Network diffusion model predicts neurodegeneration in limb-onset amyotrophic lateral sclerosis

This study uses a Network Diffusion Model to predict neurodegeneration patterns in limb-onset ALS by correlating simulated pathology spread with MRI-measured atrophy.

Rare and common variant analyses of amyotrophic lateral sclerosis in the French-Canadian genome

This study analyzes rare and common variants in ALS using French-Canadian data, finding that PRS and rare variants independently affect risk but do not interact significantly.

Novel and known transcriptional targets of ALS/FTD protein TDP-43: Meta-analysis and interactive graphical databases

The paper identifies novel and known TDP-43 targets through meta-analysis of RNA-seq data from TDP-43 knockdown models and validates them in ALS/FTD brain tissue.

Endogenous Retroviruses and TDP-43 Proteinopathy Form a Sustaining Feedback to Drive the Intercellular Spread of Neurodegeneration

The paper shows that endogenous retroviruses and TDP-43 proteinopathy form a feedback loop that drives the spread of neurodegeneration in a Drosophila model.

Changes in adenosine and neurotrophic signaling in the SOD1G93A mouse model of amyotrophic lateral sclerosis: modulation by chronic caffeine intake

This study examines adenosine and VEGF signaling changes in SOD1G93A mice with and without chronic caffeine treatment, finding early adenosinergic dysfunction and caffeine's impact on BDNF levels.

Questioning the association of the STMN2 dinucleotide repeat with ALS

The paper investigates the association between STMN2 CA repeats and ALS risk using whole genome sequencing data and finds no significant association.

Bimodal regulation of axonal transport by the GDNF-RET signalling axis in healthy and diseased motor neurons

This study shows that blocking the GDNF-RET signalling axis rescues axonal transport deficits in ALS models, suggesting it as a potential therapeutic target.

Proteomic signature and mesenchymal stromal/stem cell-derived extracellular vesicle treatment of iPSC motor neurons from different ALS patient groups

This study identifies proteomic signatures in iPSC-derived motor neurons with ALS mutations and shows MSC-EVs can reverse proteomic changes and restore neurite growth in FUS-ALS MNs.

GLT8D1 mutations cause amyotrophic lateral sclerosis via disruption of neurotrophin signalling within membrane lipid rafts

This paper identifies GLT8D1 mutations as a cause of ALS by disrupting neurotrophin signaling in lipid rafts through reduced ganglioside expression.

ALS-linked KIF5A ΔExon27 mutant causes neuronal toxicity through gain of function

This study shows that KIF5A ΔExon27 mutant causes neuronal toxicity through gain of function by forming aggregates and increasing motor activity.

Optineurin deficiency induces patchy hair loss but it is not sufficient to cause amyotrophic lateral sclerosis in mice

This study shows that optineurin deficiency in mice causes patchy hair loss but not ALS-like symptoms, suggesting other factors are needed for ALS development.

Analysis of pre-symptomatic Drosophila models for ALS and SMA reveals convergent impact on functional protein complexes linked to neuro-muscular degeneration

The paper identifies convergent functional impacts of SMA and ALS genes on neuronal protein complexes in Drosophila models, suggesting shared mechanisms in motor neuron degeneration.

TDP-43 subcellular mislocalisation is correlated with loss of optineurin binding for frontotemporal dementia and amyotrophic lateral sclerosis associated TBK1 missense variants

The paper investigates how TBK1 missense variants affect TDP-43 mislocalization and OPTN binding in FTD and ALS, finding that loss of OPTN binding is more critical than kinase activity.

Loss of Stathmin-2, a hallmark of TDP-43-associated ALS, causes motor neuropathy

This study shows that loss of STMN2, linked to TDP-43 pathology in ALS, causes motor neuropathy with NMJ denervation in mice.

Mitochondrial function determines severity but not risk of amyotrophic lateral sclerosis

The paper investigates how mitochondrial function affects ALS severity but not risk, identifying specific genetic and expression factors linked to disease progression.

Two therapeutic CRISPR/Cas9 gene editing approaches revert FTD/ALS cellular pathology caused by a C9orf72 repeat expansion mutation in patient derived cells

This study evaluates three CRISPR/Cas9 approaches to correct C9orf72 repeat expansion in patient-derived neurons, finding that repeat and mutant allele excision fully eliminate dipeptide repeats.

Sequestration of TDP-43216-414 aggregates by cytoplasmic expression of the proSAAS chaperone

This study shows that cytoplasmic proSAAS forms liquid-like condensates that sequester TDP-43 aggregates, providing cytoprotection against toxicity in yeast.

Three ALS genes regulate expression of the MHC class II antigen presentation pathway

The paper shows that ALS genes FUS, TAF15, and MATR3 regulate the MHC II antigen presentation pathway by downregulating HLA-DR and CD74 through loss of CIITA, with implications for immune system failure in ALS.

Plasma miRNA-214 is a predictive candidate biomarker of progression speed in patients with ALS

This study identifies plasma miRNA-214-3p as a biomarker predicting ALS progression speed by linking it to phagocytic dysfunction in patient-derived microglia.

Toxic SOD1 trimers are off-pathway in the formation of amyloid-like fibrils in ALS

This study shows that toxic SOD1 trimers are an off-pathway intermediate competing with protective fibril formation in ALS, and stabilizing trimers reduces larger aggregate formation.

Effects of the investigational drug sodium phenylbutyrate-TUDCA (AMX0035) on the transcriptional and metabolic landscape of sporadic ALS fibroblasts

This study examines the effects of AMX0035 on the transcriptomic and metabolomic profiles of sporadic ALS fibroblasts, finding that the combination treatment alters more genes and metabolites than individual components.

Neuronal activity regulates Matrin 3 levels and function in a calcium-dependent manner through calpain cleavage and calmodulin binding

This study shows that neuronal activity regulates MATR3 levels and function through calpain cleavage and Ca2+/calmodulin binding, linking these processes to ALS pathology.

New molecular signatures defining the differential proteostasis response in ALS-resistant and -sensitive motor neurons

The paper identifies molecular signatures of proteostasis differences between ALS-resistant and -sensitive motor neurons using transcriptome and proteome analysis.

Cell environment shapes TDP-43 function: implications in neuronal and muscle disease

The paper compares TDP-43's transcriptional and splicing effects in muscle and neuronal cells, showing tissue-specific roles in disease.

ALS sensitive spinal motor neurons enter a degenerative downward spiral of impaired splicing and proteostasis

This study identifies differences in proteostasis and splicing between ALS-resistant cranial motor neurons and ALS-sensitive spinal motor neurons derived from iPSCs.

Selective Vulnerability of Tripartite Synapses in Amyotrophic Lateral Sclerosis.

The paper investigates tripartite synapse loss in ALS models and human tissue, finding selective vulnerability of these synapses in both mice and humans.

pTDP-43 aggregates accumulate in the gut and other non-central nervous system tissues prior to symptom onset in amyotrophic lateral sclerosis

The paper identifies pTDP-43 aggregates in non-CNS tissues of ALS patients prior to symptom onset, suggesting systemic pathology beyond the central nervous system.

Unique molecular features and cellular responses differentiate two populations of motor cortical layer 5b neurons in a preclinical model of ALS.

The paper identifies molecular differences between two populations of motor cortical layer 5b neurons in an ALS model, showing Oxphos pathway regulation and reactive oxygen species handling as factors in selective degeneration.

ALS monocyte-derived microglia reveal cytoplasmic TDP-43 accumulation, DNA damage, and cell-specific impairment of phagocytosis associated with disease progression.

This paper develops a method to generate monocyte-derived microglia from ALS patient blood, revealing functional impairments and pathological features associated with disease progression.

TDP-43 represses cryptic exon inclusion in FTD/ALS gene UNC13A

This study shows that TDP-43 represses a cryptic exon in UNC13A, and genetic variants associated with FTD/ALS increase cryptic exon inclusion when TDP-43 is dysfunctional.