ArticleNature communications2020
Optogenetic modulation of TDP-43 oligomerization accelerates ALS-related pathologies in the spinal motor neurons.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- TDP-43 proteinopathy as a biomarker and therapeutic target in amyotrophic lateral sclerosis.Biochemical Society transactions · 2026Review
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- TARDBP (TDP-43) Knock-in Zebrafish Display a Late-Onset Motor Phenotype and Loss of Large Spinal Cord Motor Neurons.Annals of neurology · 2026Article
- Human TDP-43 overexpression in zebrafish motor neurons triggers MND-like phenotypes through gain-of-function mechanism.Acta neuropathologica communications · 2025Article
- Quantitative Profiling of Nanoscopic Protein Aggregates Reveals Specific Fingerprint of TDP-43-Positive Assemblies in Motor Neuron Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Intrinsically accelerated cellular degradation is amplified by TDP-43 loss in ALS-vulnerable motor neurons in a zebrafish model.Nature communications · 2025Article
- Biallelic variants in DNAJC7 cause familial amyotrophic lateral sclerosis with the TDP-43 pathology.Acta neuropathologica · 2025Article
- Optogenetics to biomolecular phase separation in neurodegenerative diseases.Molecules and cells · 2025Review
- Critical impact of lysine 136 in TDP-43 phase separation, compartmentalization, and aggregation in living vertebrates.iScience · 2025Article
- Zebrafish metabolomics: a comprehensive approach to understanding health and disease.Functional & integrative genomics · 2025Review
- Optogenetic induction of TDP-43 aggregation impairs neuronal integrity and behavior in Caenorhabditis elegans.Translational neurodegeneration · 2025Article
- RNA granules in flux: dynamics to balance physiology and pathology.Nature reviews. Neuroscience · 2024Review
- Application of Optogenetics in Neurodegenerative Diseases.Cellular and molecular neurobiology · 2024Review
- RNA-binding properties orchestrate TDP-43 homeostasis through condensate formation in vivo.Nucleic acids research · 2024Article
- Drug Screening and Validation Targeting TDP-43 Proteinopathy for Amyotrophic Lateral Sclerosis.Aging and disease · 2024Review
- Recombinant Full-Length TDP-43 Oligomers Retain Their Ability to Bind RNAs, Are Not Toxic, and Do Not Seed TDP-43 Aggregation in Vitro.ACS chemical neuroscience · 2024Article
- In Vivo Optogenetic Phase Transition of an Intrinsically Disordered Protein.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Dysregulated TDP-43 proteostasis perturbs excitability of spinal motor neurons during brainstem-mediated fictive locomotion in zebrafish.Development, growth & differentiation · 2023Article
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3 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Cytoplasmic aggregation of TDP-43 characterizes degenerating neurons in most cases of amyotrophic lateral sclerosis (ALS). Here, we develop an optogenetic TDP-43 variant (opTDP-43), whose multimerization status can be modulated in vivo through external light illumination. Using the translucent zebrafish neuromuscular system, we demonstrate that short-term light stimulation reversibly induces cytoplasmic opTDP-43 mislocalization, but not aggregation, in the spinal motor neuron, leading to an axon outgrowth defect associated with myofiber denervation. In contrast, opTDP-43 forms pathological aggregates in the cytoplasm after longer-term illumination and seeds non-optogenetic TDP-43 aggregation. Furthermore, we find that an ALS-linked mutation in the intrinsically disordered region (IDR) exacerbates the light-dependent opTDP-43 toxicity on locomotor behavior. Together, our results propose that IDR-mediated TDP-43 oligomerization triggers both acute and long-term pathologies of motor neurons, which may be relevant to the pathogenesis and progression of ALS.
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