ArticleProceedings of the National Academy of Sciences of the United States of America2020
TDP-43 dysfunction restricts dendritic complexity by inhibiting CREB activation and altering gene expression.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Genome-Wide Gene-Set Analysis Identifies Molecular Mechanisms Associated with ALS.International journal of molecular sciences · 2023Pooled it
- Human TDP-43 expression worsens FTD-related phenotypes in progranulin-insufficient mice.Neurobiology of disease · 2026Article
- Predictive Cellular Signatures from Live Human Motor Neurons Distinguish TDP-43 ALS and Enable ALS Subtype Stratification.bioRxiv : the preprint server for biology · 2026Article
- Systematic characterization of the composition and dynamics of processing body-associated mRNAs.Nature communications · 2025Article
- RNA Granules at the Crossroads of Synaptic Dysfunction and Neurodegeneration.Journal of neurochemistry · 2025Review
- Decoding TDP-43: the molecular chameleon of neurodegenerative diseases.Acta neuropathologica communications · 2024Review
- Early disruption of the CREB pathway drives dendritic morphological alterations in FTD/ALS cortical neurons.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Nicotinamide Adenine Dinucleotide Precursor Supplementation Modulates Neurite Complexity and Survival in Motor Neurons from Amyotrophic Lateral Sclerosis Models.Antioxidants & redox signaling · 2024Article
- cAMP/PKA signaling regulates TDP-43 aggregation and mislocalization.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Connectome-based modelling of neurodegenerative diseases: towards precision medicine and mechanistic insight.Nature reviews. Neuroscience · 2023Review
- Comparison of TRIBE and STAMP for identifying targets of RNA binding proteins in human andRNA (New York, N.Y.) · 2023Article
- Identification of RNA-Binding Protein Targets with HyperTRIBE inInternational journal of molecular sciences · 2023Article
- Article
- Limbic-Predominant Age-Related TDP-43 Encephalopathy: LATE-Breaking Updates in Clinicopathologic Features and Biomarkers.Current neurology and neuroscience reports · 2022Review
- The Role of TDP-43 in Neurodegenerative Disease.Molecular neurobiology · 2022Review
- Pum2 and TDP-43 refine area-specific cytoarchitecture post-mitotically and modulate translation ofeLife · 2022Article
- Targeted RNA editing: novel tools to study post-transcriptional regulation.Molecular cell · 2022Review
- Liquid-Liquid Phase Separation of TDP-43 and FUS in Physiology and Pathology of Neurodegenerative Diseases.Frontiers in molecular biosciences · 2022Review
- Synaptic dysfunction in ALS and FTD: anatomical and molecular changes provide insights into mechanisms of disease.Frontiers in molecular neuroscience · 2022Review
- Investigating Fractal Analysis as a Diagnostic Tool That Probes the Connectivity of Hippocampal Neurons.Frontiers in physiology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two related neurodegenerative diseases that present with similar TDP-43 pathology in patient tissue. TDP-43 is an RNA-binding protein which forms aggregates in neurons of ALS and FTD patients as well as in a subset of patients diagnosed with other neurodegenerative diseases. Despite our understanding that TDP-43 is essential for many aspects of RNA metabolism, it remains obscure how TDP-43 dysfunction contributes to neurodegeneration. Interestingly, altered neuronal dendritic morphology is a common theme among several neurological disorders and is thought to precede neurodegeneration. We previously found that both TDP-43 overexpression (OE) and knockdown (KD) result in reduced dendritic branching of cortical neurons. In this study, we used TRIBE (targets of RNA-binding proteins identified by editing) as an approach to identify signaling pathways that regulate dendritic branching downstream of TDP-43. We found that TDP-43 RNA targets are enriched for pathways that signal to the CREB transcription factor. We further found that TDP-43 dysfunction inhibits CREB activation and CREB transcriptional output, and restoring CREB signaling rescues defects in dendritic branching. Finally, we demonstrate, using RNA sequencing, that TDP-43 OE and KD cause similar changes in the abundance of specific messenger RNAs, consistent with their ability to produce similar morphological defects. Our data therefore provide a mechanism by which TDP-43 dysfunction interferes with dendritic branching, and may define pathways for therapeutic intervention in neurodegenerative diseases.
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