ArticleScientific reports2019
TDP-43 aggregation inside micronuclei reveals a potential mechanism for protein inclusion formation in ALS.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 28 citations in OpenAlex.
- Loss of Y chromosome and its implications in male amyotrophic lateral sclerosis: insights from the UK Biobank.BMC medicine · 2025Article
- Role of autophagy in neurotoxic protein's clearance following post-ischemic stroke: where we are and what we know?Molecular brain · 2025Review
- Co-Aggregation of TDP-43 with Other Pathogenic Proteins and Their Co-Pathologies in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Article
- Mitigation of TDP-43 toxic phenotype by an RGNEF fragment in amyotrophic lateral sclerosis models.Brain : a journal of neurology · 2024Article
- Epigenetics in the formation of pathological aggregates in amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2024Review
- 5-Hydroxytryptamine: a potential therapeutic target in amyotrophic lateral sclerosis.Neural regeneration research · 2023Article
- Novel rAAV vector mediated intrathecal HGF delivery has an impact on neuroimmune modulation in the ALS motor cortex with TDP-43 pathology.Gene therapy · 2023Article
- Tandem detergent-extraction and immunoprecipitation of proteinopathy: Scalable enrichment of ALS-associated TDP-43 aggregates.iScience · 2023Article
- Mitochondrial dysregulation occurs early in ALS motor cortex with TDP-43 pathology and suggests maintaining NADScientific reports · 2022Article
- Protein Aggregation in the Pathogenesis of Ischemic Stroke.Cellular and molecular neurobiology · 2021Review
- The Different Faces of the TDP-43 Low-Complexity Domain: The Formation of Liquid Droplets and Amyloid Fibrils.International journal of molecular sciences · 2021Review
- Protein Aggregation Landscape in Neurodegenerative Diseases: Clinical Relevance and Future Applications.International journal of molecular sciences · 2021Review
- Genome instability and loss of protein homeostasis: converging paths to neurodegeneration?Open biology · 2021Review
- The Integral Role of RNA in Stress Granule Formation and Function.Frontiers in cell and developmental biology · 2021Review
- Inclusion Formation and Toxicity of the ALS Protein RGNEF and Its Association with the Microtubule Network.International journal of molecular sciences · 2020Article
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease with no known etiology. The formation of pathological protein inclusions, including RNA-binding proteins such as TDP-43 and rho guanine nucleotide exchange factor (RGNEF) are a hallmark of ALS. Despite intensive research, the mechanisms behind protein aggregate formation in ALS remains unclear. We have investigated the role of metabolic stress in protein aggregate formation analyzing how it is relevant to the co-aggregation observed between RGNEF and TDP-43 in motor neurons of ALS patients. Metabolic stress was able to induce formation of micronuclei, small nuclear fragments, in cultured cells. Notably, we observed the formation TDP-43 protein inclusions within micronuclei that co-aggregate with RGNEF and can be released to the cytoplasm. We observed that the leucine-rich domain of RGNEF is critical for its interaction with TDP-43 and localization in micronuclei. Finally, we described that micronuclei-like structures can be found in brain and spinal cord of ALS patients. This work is the first description of protein inclusion formation within micronuclei which also is linked with a neurodegenerative disease. The formation of TDP-43 inclusions within micronuclei induced by metabolic stress is a novel mechanism of protein aggregate formation which may have broad relevance for ALS and other neurodegenerative diseases.
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