ArticleThe Journal of biological chemistry2016
Familial Amyotrophic Lateral Sclerosis-linked Mutations in Profilin 1 Exacerbate TDP-43-induced Degeneration in the Retina of Drosophila melanogaster through an Increase in the Cytoplasmic Localization of TDP-43.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 19 citations in OpenAlex.
- Viral-mediated knockdown of Atxn2 attenuates TDP-43 pathology and muscle dysfunction in the PFN1Acta neuropathologica communications · 2025Article
- TDP-43 as a potential retinal biomarker for neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- The Role of Gene Expression Dysregulation in the Pathogenesis of Mucopolysaccharidosis: A Comparative Analysis of Shared and Specific Molecular Markers in Neuronopathic and Non-Neuronopathic Types of the Disease.International journal of molecular sciences · 2024Article
- iPSC motor neurons, but not other derived cell types, capture gene expression changes in postmortem sporadic ALS motor neurons.Cell reports · 2023Article
- Multiple roles for the cytoskeleton in ALS.Experimental neurology · 2022Review
- The E50K optineurin mutation impacts autophagy-mediated degradation of TDP-43 and leads to RGC apoptosis in vivo and in vitro.Cell death discovery · 2021Article
- Profilin Isoforms in Health and Disease - All the Same but Different.Frontiers in cell and developmental biology · 2021Review
- The role of DNA damage response in amyotrophic lateral sclerosis.Essays in biochemistry · 2020Review
- The Peripheral Nervous System in Amyotrophic Lateral Sclerosis: Opportunities for Translational Research.Frontiers in neuroscience · 2019Review
- Changes in biophysical characteristics of PFN1 due to mutation causing amyotrophic lateral sclerosis.Metabolic brain disease · 2018Article
- The ALS-inducing factors, TDP43Scientific reports · 2018Article
- The physiological and pathological biophysics of phase separation and gelation of RNA binding proteins in amyotrophic lateral sclerosis and fronto-temporal lobar degeneration.Brain research · 2018Review
- Stability of an aggregation-prone partially folded state of human profilin-1 correlates with aggregation propensity.The Journal of biological chemistry · 2018Article
- Robustness and Vulnerability of the Autoregulatory System That Maintains Nuclear TDP-43 Levels: A Trade-off Hypothesis for ALS Pathology Based onFrontiers in neuroscience · 2018Article
- Profilin Directly Promotes Microtubule Growth through Residues Mutated in Amyotrophic Lateral Sclerosis.Current biology : CB · 2017Article
- A Drosophila model of ALS reveals a partial loss of function of causative human PFN1 mutants.Human molecular genetics · 2017Article
- Protein Quality Control and the Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Continuum.Frontiers in molecular neuroscience · 2017Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive and selective loss of motor neurons. Causative genes for familial ALS (fALS), e.g. TARDBP or FUS/TLS, have been found, among which mutations within the profilin 1 (PFN1) gene have recently been identified in ALS18. To elucidate the mechanism whereby PFN1 mutations lead to neuronal death, we generated transgenic Drosophila melanogaster overexpressing human PFN1 in the retinal photoreceptor neurons. Overexpression of wild-type or fALS mutant PFN1 caused no degenerative phenotypes in the retina. Double overexpression of fALS mutant PFN1 and human TDP-43 markedly exacerbated the TDP-43-induced retinal degeneration, i.e. vacuolation and thinning of the retina, whereas co-expression of wild-type PFN1 did not aggravate the degenerative phenotype. Notably, co-expression of TDP-43 with fALS mutant PFN1 increased the cytoplasmic localization of TDP-43, the latter remaining in nuclei upon co-expression with wild-type PFN1, whereas co-expression of TDP-43 lacking the nuclear localization signal with the fALS mutant PFN1 did not aggravate the retinal degeneration. Knockdown of endogenous Drosophila PFN1 did not alter the degenerative phenotypes of the retina in flies overexpressing wild-type TDP-43 These data suggest that ALS-linked PFN1 mutations exacerbate TDP-43-induced neurodegeneration in a gain-of-function manner, possibly by shifting the localization of TDP-43 from nuclei to cytoplasm.
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