Amyotrophic Lateral Sclerosis Research

Lipid Dysregulation Unveil the Intricate Interplay of Lysosomal and Mitochondrial Changes in Frontotemporal Dementia with GRN Haploinsufficiency

This study shows that GRN haploinsufficiency in FTD causes lysosomal and mitochondrial dysfunction, lipid metabolism changes, and autophagy impairment, which may contribute to disease pathogenesis.

TDP-43 dysregulation of polyadenylation site selection is a defining feature of RNA misprocessing in ALS/FTD and related disorders

The paper identifies TDP-43 dysregulation of polyadenylation site selection as a key feature of RNA misprocessing in ALS/FTD and related disorders, linking it to increased tau phosphorylation.

TDP-43 loss induces extensive cryptic polyadenylation in ALS/FTD

The paper identifies novel cryptic polyadenylation events induced by TDP-43 loss in ALS/FTD using bioinformatic methods and shows their potential disease relevance and impact on protein translation.

The shared ancestry between the C9orf72 hexanucleotide repeat expansion and intermediate-length alleles using haplotype sharing trees and HAPTK

The paper uses haplotype sharing trees and HAPTK to show that intermediate-length C9orf72 repeat alleles share haplotypes with the hexanucleotide repeat expansion, suggesting they are potential premutation alleles.

Novel FKBP12 ligand promotes functional improvement in SOD1-G93A ALS mice

This study tests a novel FKBP12 ligand, MP-010, in ALS mice, showing improved motor function, preserved motor neurons, and extended lifespan.

Enhanced legumain activity links progranulin deficiency to TDP-43 pathology in frontotemporal lobar degeneration

This study shows that reduced progranulin leads to increased legumain activity, which promotes TDP-43 pathology in FTLD, suggesting legumain as a therapeutic target.

Dysregulated expanded endocannabinoid system as therapeutic targets of amyotrophic lateral sclerosis

The paper identifies dysregulated expanded endocannabinoid system metabolites in ALS and shows FAAH inhibition improves motor neuron degeneration in models.

Scalable, optically-responsive human neuromuscular junction model reveals convergent mechanisms of synaptic dysfunction in familial ALS

This study develops a human neuromuscular junction model from pluripotent stem cells to investigate synaptic dysfunction in familial ALS and assess therapeutic candidates.

ALS patient-derived motor neuron networks exhibit microscale dysfunction and mesoscale compensation rendering them highly vulnerable to perturbation

The paper shows ALS patient-derived motor neuron networks develop cytopathology and form efficient networks with functional impairments and heightened vulnerability to perturbation.

Deep Learning Analysis on Images of iPSC-derived Motor Neurons Carrying fALS-genetics Reveals Disease-Relevant Phenotypes

The paper uses deep learning on images of iPSC-derived motor neurons with fALS mutations to identify disease-relevant phenotypes and molecular differences.

Protein Assembly Modulation: A New Approach to ALS Therapeutics

This paper introduces a new drug-like small molecule series targeting PDI in a multi-protein complex for ALS treatment, showing activity in cellular and animal models.

ALS iPSC-derived microglia and motor neurons respond to astrocyte-targeted IL-10 and CCL2 modulation

The paper tests astrocyte-targeted IL-10 and CCL2 modulation in ALS iPSC models, finding reduced neuroinflammation and altered microglia/motor neuron responses in co-cultures.

Highly variable molecular signatures of TDP-43 loss of function are associated with nuclear pore complex injury in a population study of sporadic ALS patient iPSNs

Axon guidance genes are regulated by TDP-43 and RGNEF through the rate of long-intron processing.

The paper shows TDP-43 and RGNEF regulate axon guidance genes through their opposing effects on long-intron processing in neuronal-like cells.

A multi-omics dataset for the analysis Frontotemporal Dementia genetic subtypes

The paper presents a multi-omics dataset for genetic subtypes of frontotemporal dementia to identify molecular mechanisms disrupted in the disease.

Somatic mosaicism in amyotrophic lateral sclerosis and frontotemporal dementia identifies focal mutations associated with widespread degeneration

The paper identifies rare somatic mutations in sporadic ALS and FTD cases, suggesting they contribute to disease and widespread neurodegeneration.

The ALS-associated TDP-43M337V mutation dysregulates microglia-derived extracellular microRNAs in a sex-specific manner

This study shows that the TDP-43M337V mutation in microglia alters miRNA release in a sex-specific way, potentially affecting ALS progression.

Pathogenic TDP-43 Disrupts Axon Initial Segment Structure and Neuronal Excitability in a Human iPSC Model of ALS

This study shows that TDP-43G298S mutations in human iPSC-derived motor neurons alter axon initial segment structure and neuronal excitability at different developmental stages.

A deep-learning-based screening platform in aging-relevant human motor neurons to identify therapeutic compounds for amyotrophic lateral sclerosis

The paper develops a deep learning platform to screen compounds for ALS treatment using age-relevant human motor neurons and identifies NCB-0846 as a potential therapeutic.

Antisense oligonucleotides targeting the miR-29b binding site in the GRN mRNA increase progranulin translation

This study shows that antisense oligonucleotides can increase progranulin protein levels by blocking miR-29b binding in GRN mRNA, offering a potential therapy for FTD.

Injectable borax-loaded alginate hydrogels reduce muscle atrophy, modulate inflammation, and generate neuroprotection in the SOD1G93A mouse model of ALS via activation of the IGF-Akt-mTOR axis pathway.

The paper demonstrates that injectable borax-loaded alginate hydrogels improve motor function and survival in SOD1G93A mice by activating the IGF-Akt-mTOR pathway in muscle, reducing atrophy and inflammation.

Two neuronal models of TDP-43 proteinopathy display reduced axonal translation, increased oxidative stress, and defective exocytosis.

This study characterizes two TDP-43 proteinopathy models in mouse neurons, revealing reduced axonal translation, increased oxidative stress, and presynaptic dysfunction linked to mRNA metabolism disruption.

TNFa hinders FGF4 efficacy to mitigate ALS astrocyte dysfunction and cGAS-STING pathway-induced innate immune reactivity

This study shows that FGF4 reduces ALS astrocyte reactivity but fails to protect motor neurons in a mouse model, while TNF exacerbates astrocyte dysfunction.

Ggnbp2 regulates synaptic development and autophagy in motor neurons

This study investigates the function of the ALS risk variant GGNBP2 in Drosophila motor neurons, showing it regulates autophagy and synaptic development.

RNA aptamer reveals nuclear TDP-43 pathology is an early aggregation event that coincides with STMN-2 cryptic splicing and precedes clinical manifestation in ALS

This study uses an RNA aptamer to detect TDP-43 aggregation and shows that nuclear TDP-43 pathology and STMN-2 cryptic splicing occur before clinical symptoms in ALS.

C9ORF72 deficiency results in degeneration of the zebrafish retina in vivo

This study shows that C9ORF72 deficiency in zebrafish causes retinal degeneration, including reduced thickness, gliosis, and neuronal loss, but not spinal cord pathology.

Early nuclear phenotypes and reactive transformation in human iPSC-derived astrocytes from ALS patients with SOD1 mutations

This study identifies early nuclear phenotypes in SOD1-mutated astrocytes derived from ALS patients that precede reactive transformation and may affect astrocyte-MN communication.

Rare variant analyses validate known ALS genes in a multi-ethnic population and identifies ANTXR2 as a candidate in PLS

Mitigation of TDP-43-induced toxic phenotype by expression of RGNEF N-terminal fragment in ALS models

This study shows that expressing a RGNEF N-terminal fragment mitigates TDP-43 toxicity in ALS models by reducing aggregation and neurodegeneration.

Divergent Molecular Pathways for Toxicity of Selected Mutant C9ORF72-derived Dipeptide Repeats

This study identifies compartment-specific toxic effects of C9ORF72-derived dipeptide repeats (DPRs) in neurodegenerative disease models, revealing two distinct pathogenic mechanisms contributing to ALS and FTD.