ArticleNeuropathology : official journal of the Japanese Society of Neuropathology2020
Praja1 RING-finger E3 ubiquitin ligase suppresses neuronal cytoplasmic TDP-43 aggregate formation.
Article in Neuropathology : official journal of the Japanese Society of Neuropathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- E3 ligase Praja1 mediates ubiquitination and degradation of microtubule-associated protein tau.The FEBS journal · 2026Article
- Ubiquitin-specific peptidase-19 links TDP-43 aggregation to ER stress.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The E3 Ubiquitin Ligase PRAJA1: A Key Regulator of Synaptic Dynamics and Memory Processes with Implications for Alzheimer's Disease.International journal of molecular sciences · 2025Article
- Functional constraints of wtf killer meiotic drivers.PLoS genetics · 2025Article
- Ubiquitin-Proteasome-Mediated Protein Degradation and Disorders of the Central Nervous System.International journal of molecular sciences · 2025Review
- Functional constraints ofbioRxiv : the preprint server for biology · 2025Article
- Prion-like Spreading of Disease in TDP-43 Proteinopathies.Brain sciences · 2024Review
- Article
- Asian-European differentiation of schizophrenia-associated genes driven by admixture and natural selection.iScience · 2024Article
- The pathogenic mechanism of TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis.Neural regeneration research · 2024Review
- Loss of TDP-43 mediates severe neurotoxicity by suppressing PJA1 gene transcription in the monkey brain.Cellular and molecular life sciences : CMLS · 2024Article
- Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders.Molecular neurobiology · 2023Review
- PJA1 mediates the effects of astrocytic GPR30 on learning and memory in female mice.The Journal of clinical investigation · 2023Article
- CRISPR/Cas-Based Approaches to Study Schizophrenia and Other Neurodevelopmental Disorders.International journal of molecular sciences · 2022Review
- Praja1 RING-finger E3 ubiquitin ligase is a common suppressor of neurodegenerative disease-associated protein aggregation.Neuropathology : official journal of the Japanese Society of Neuropathology · 2022Article
- Gel-like inclusions of C-terminal fragments of TDP-43 sequester stalled proteasomes in neurons.EMBO reports · 2022Article
- Article
- Functional implication of ubiquitinating and deubiquitinating mechanisms in TDP-43 proteinopathies.Frontiers in cell and developmental biology · 2022Review
- Praja1 ubiquitin ligase facilitates degradation of polyglutamine proteins and suppresses polyglutamine-mediated toxicity.Molecular biology of the cell · 2021Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Transactivation response DNA-binding protein of 43 kDa (TDP-43) is a major constituent of cytoplasmic aggregates in neuronal and glial cells in cases of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We have previously shown neuronal cytoplasmic aggregate formation induced by recombinant adenoviruses expressing human wild-type and C-terminal fragment (CTF) TDP-43 under the condition of proteasome inhibition in vitro and in vivo. In the present study, we demonstrated that the formation of the adenoviral TDP-43 aggregates was markedly suppressed in rat neural stem cell-derived neuronal cells by co-infection of an adenovirus expressing heat shock transcription factor 1 (HSF1), a master regulator of heat shock response. We performed DNA microarray analysis and searched several candidate molecules, located downstream of HSF1, which counteract TDP-43 aggregate formation. Among these, we identified Praja 1 RING-finger E3 ubiquitin ligase (PJA1) as a suppressor of phosphorylation and aggregate formation of TDP-43. Co-immunoprecipitation assay revealed that PJA1 binds to CTF TDP-43 and the E2-conjugating enzyme UBE2E3. PJA1 also suppressed formation of cytoplasmic phosphorylated TDP-43 aggregates in mouse facial motor neurons in vivo. Furthermore, phosphorylated TDP-43 aggregates were detected in PJA1-immunoreactive human ALS motor neurons. These results indicate that PJA1 is one of the principal E3 ubiquitin ligases for TDP-43 to counteract its aggregation propensity and could be a potential therapeutic target for ALS and FTLD.
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