ArticleJournal of neuroinflammation2020
The overexpression of TDP-43 in astrocytes causes neurodegeneration via a PTP1B-mediated inflammatory response.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 59 citations in OpenAlex.
- Extracellular Vesicle Packaged TDP43 Derived From ECs Exacerbates Cigarette Tar-Related Atherosclerosis Progression via Enhancing Macrophage Extracellular Traps.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TDP-43-immunity-microbiota axis in amyotrophic lateral sclerosis: A potential pathogenic mechanism.Neural regeneration research · 2026Article
- Targeting astrocyte-mediated neurotoxicity induced by ALS/FTD-associated RNA binding proteins.Cell communication and signaling : CCS · 2026Article
- Poncirin Alleviates Hypoxic Pulmonary Hypertension by Blocking TDP43-Mediated Macrophage Pyroptosis.Pulmonary circulation · 2026Article
- Fos regulates age-dependent neuroinflammation in a VAPP58S model of amyotrophic lateral sclerosis.Disease models & mechanisms · 2026Article
- Loss of TDP-43 Drives Innate Immune Activation Through Relish inInternational journal of molecular sciences · 2026Article
- PTP1B in astrocytes drives pathogen-induced neurodegeneration.Journal of neuroinflammation · 2026Article
- Elucidation of Molecular Mechanisms of Lipid-Altered Cytotoxicity of TDP-43 Fibrils.ACS chemical neuroscience · 2026Article
- Amyloid beta pathology induces astrocytic pTDP-43 mislocalization and disrupts TDP-43-regulated cryptic exon transcripts.Frontiers in aging neuroscience · 2026Article
- Spatiotemporal Dynamics and Cellular States of Neuroinflammation in Amyotrophic Lateral Sclerosis: Implications for Stage‑Specific Therapeutics.ASN neuro · 2026Review
- Exploration of biomaterial and stem cell-based strategies for promoting neuronal regeneration and creating engineered 3D in-vitro disease models.Journal of translational medicine · 2025Review
- Novel Dual Mechanism GRT-X Agonist Acting on Kv7 Potassium Channel/Translocator Protein Receptor Prevents Motoneuron Degeneration Following Exposure to Mouse and Human Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Astrocyte-Conditioned Media.ACS chemical neuroscience · 2025Article
- Neuroimmune signaling mediates astrocytic nucleocytoplasmic disruptions and stress granule formation associated with TDP-43 pathology.Neurobiology of disease · 2025Article
- Review
- Endogenous TDP-43 mislocalization in a novel knock-in mouse model reveals DNA repair impairment, inflammation, and neuronal senescence.Acta neuropathologica communications · 2025Article
- Perivascular phosphorylated TDP-43 inclusions are associated with Alzheimer's disease pathology and loss of CD146 and Aquaporin-4.Brain pathology (Zurich, Switzerland) · 2025Article
- Drosophila glial system: an approach towards understanding molecular complexity of neurodegenerative diseases.Molecular biology reports · 2024Review
- Potential Mechanisms of Tunneling Nanotube Formation and Their Role in Pathology Spread in Alzheimer's Disease and Other Proteinopathies.International journal of molecular sciences · 2024Review
- Cellular and molecular mechanisms of the blood-brain barrier dysfunction in neurodegenerative diseases.Fluids and barriers of the CNS · 2024Review
- A pathologic study of Perivascular pTDP-43 Lin bodies in LATE-NC.Acta neuropathologica communications · 2024Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundCytoplasmic inclusions of transactive response DNA binding protein of 43 kDa (TDP-43) in neurons and astrocytes are a feature of some neurodegenerative diseases, such as frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) and amyotrophic lateral sclerosis (ALS). However, the role of TDP-43 in astrocyte pathology remains largely unknown.
methodsTo investigate whether TDP-43 overexpression in primary astrocytes could induce inflammation, we transfected primary astrocytes with plasmids encoding Gfp or TDP-43-Gfp. The inflammatory response and upregulation of PTP1B in transfected cells were examined using quantitative RT-PCR and immunoblot analysis. Neurotoxicity was analysed in a transwell coculture system of primary cortical neurons with astrocytes and cultured neurons treated with astrocyte-conditioned medium (ACM). We also examined the lifespan, performed climbing assays and analysed immunohistochemical data in pan-glial TDP-43-expressing flies in the presence or absence of a Ptp61f RNAi transgene.
resultsPTP1B inhibition suppressed TDP-43-induced secretion of inflammatory cytokines (interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)) in primary astrocytes. Using a neuron-astrocyte coculture system and astrocyte-conditioned media treatment, we demonstrated that PTP1B inhibition attenuated neuronal death and mitochondrial dysfunction caused by overexpression of TDP-43 in astrocytes. In addition, neuromuscular junction (NMJ) defects, a shortened lifespan, inflammation and climbing defects caused by pan-glial overexpression of TDP-43 were significantly rescued by downregulation of ptp61f (the Drosophila homologue of PTP1B) in flies.
conclusionsThese results indicate that PTP1B inhibition mitigates the neuronal toxicity caused by TDP-43-induced inflammation in mammalian astrocytes and Drosophila glial cells.
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