Amyotrophic Lateral Sclerosis Research

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

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

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.

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

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.

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

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.

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.

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

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

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

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

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

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.

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.

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

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.

This study uses a Network Diffusion Model to show that structural brain networks drive pathological spread in ALS, with seed regions in basal ganglia, thalamus, and insula, not the primary motor cortex.

The paper identifies differential regulation of specific granulin peptides and their glycosylation patterns in relation to lysosomal protease activity and physiological/pathological conditions.

This study shows that low-level overexpression of wild-type TDP-43 in mice causes late-onset, progressive neurodegeneration and paralysis, mimicking aspects of ALS and other TDP-43-related disorders.

The paper identifies TMEM106B, not TDP-43, as the protein composing amyloid fibrils in FTLD-TDP using cryo-EM.

The paper investigates the effects of AMD3100 and exogenous lactate on SOD1G93A mice, showing reduced neuroinflammation and improved remyelination without extending lifespan.

This study investigates the role of the NLRP3 inflammasome in C9orf72 FTD/ALS pathogenesis, finding that its inhibition improves survival and reduces neurodegeneration.

This study investigates how microglia and astrocytes affect neurofilament accumulation in ALS iPSC-derived motor neurons, showing glial-secreted factors influence neurofilament pathology.

This study identifies 690 candidate ALS genes using a hierarchical Bayesian model, highlighting genetic convergence on the distal axon and functional significance in motor neurons.

The paper identifies a hippocampal protein aggregation signature that distinguishes pathogenic from wildtype UBQLN2 in ALS/FTD cases.

This paper shows edaravone protects mRNA-induced motor neurons from neurotoxicity by activating the GDNF/RET signaling pathway and can replace neurotrophic factors for neuron survival.

The paper identifies constitutively active SARM1 variants in ALS patients that induce neuropathy and neuroinflammation in mice.

The paper examines age-dependent changes in inhibitory terminals and GABA inhibition in SOD1G93A ALS mouse motor neurons, finding reduced GAD67 terminals and ambient GABA inhibition in vulnerable motor pools.

The paper develops a human iPSC-derived neural model to study TDP-43 pathology, identifying NPTX2 misregulation as a key factor in ALS/FTLD neurotoxicity.