ArticleHuman molecular genetics2020
Motor neuron translatome reveals deregulation of SYNGR4 and PLEKHB1 in mutant TDP-43 amyotrophic lateral sclerosis models.
Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Integrative Structural Bioinformatics and Molecular Dynamics Analyses of Synaptic Vesicle Proteins and Their Water-Soluble QTY-Variants Reveal Membrane Constraints and Evolutionary Coupling of T ⇔ V.Journal of molecular evolution · 2026Article
- Pan-cancer multi-omics analysis identifies SYNGR4 as a novel clinical prognostic biomarker and therapeutic target in lung adenocarcinoma.Discover oncology · 2026Article
- Efficient in vivo targeting of the myocardial scar using Moloney murine leukaemia virus complexed with nanoparticles.The Journal of physiology · 2026Article
- Transcriptome-based screening in TARDBP/TDP-43 knock-in motor neurons identifies the NEDD8-activating enzyme inhibitor MLN4924.Scientific reports · 2025Article
- Immune-related genes can accurately predict survival in bladder cancer: a retrospective study via two independent immunotherapy cohorts.Translational andrology and urology · 2025Article
- Folate-mediated transgenerational inheritance of sperm DNA methylation patterns correlate with spinal axon regeneration.Epigenetics · 2024Article
- Phosphatidylserine-dependent structure of synaptogyrin remodels the synaptic vesicle membrane.Nature structural & molecular biology · 2023Article
- TDP-43 dysregulation and neuromuscular junction disruption in amyotrophic lateral sclerosis.Translational neurodegeneration · 2022Review
- Mitochondrial dysregulation occurs early in ALS motor cortex with TDP-43 pathology and suggests maintaining NADScientific reports · 2022Article
- SYNGR4 and PLEKHB1 deregulation in motor neurons of amyotrophic lateral sclerosis models: potential contributions to pathobiology.Neural regeneration research · 2022Review
- Dysregulation of Translation in TDP-43 Proteinopathies: Deficits in the RNA Supply Chain and Local Protein Production.Frontiers in neuroscience · 2022Review
- Article
- Molecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD.International journal of molecular sciences · 2021Review
- Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis.International journal of molecular sciences · 2020Article
- Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) is an incurable neurological disease with progressive loss of motor neuron (MN) function in the brain and spinal cord. Mutations in TARDBP, encoding the RNA-binding protein TDP-43, are one cause of ALS, and TDP-43 mislocalization in MNs is a key pathological feature of >95% of ALS cases. While numerous studies support altered RNA regulation by TDP-43 as a major cause of disease, specific changes within MNs that trigger disease onset remain unclear. Here, we combined translating ribosome affinity purification (TRAP) with RNA sequencing to identify molecular changes in spinal MNs of TDP-43-driven ALS at motor symptom onset. By comparing the MN translatome of hTDP-43A315T mice to littermate controls and to mice expressing wild type hTDP-43, we identified hundreds of mRNAs that were selectively up- or downregulated in MNs. We validated the deregulated candidates Tex26, Syngr4, and Plekhb1 mRNAs in an independent TRAP experiment. Moreover, by quantitative immunostaining of spinal cord MNs, we found corresponding protein level changes for SYNGR4 and PLEKHB1. We also observed these changes in spinal MNs of an independent ALS mouse model caused by a different patient mutant allele of TDP-43, suggesting that they are general features of TDP-43-driven ALS. Thus, we identified SYNGR4 and PLEKHB1 to be deregulated in MNs at motor symptom onset in TDP-43-driven ALS models. This spatial and temporal pattern suggests that these proteins could be functionally important for driving the transition to the symptomatic phase of the disease.
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