ArticlePloS one2014
Mitochondrial complex 1 inhibition increases 4-repeat isoform tau by SRSF2 upregulation.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- GV1001 reduces pathological 4R tau and functional deficits in models relevant to progressive supranuclear palsy.Scientific reports · 2026Article
- Exploring the neuroprotective potential of Nrf2-pathway activators against annonacin toxicity.Scientific reports · 2024Article
- The Roles of White Adipose Tissue and Liver NADPH in Dietary Restriction-Induced Longevity.Antioxidants (Basel, Switzerland) · 2024Review
- Posttranscriptional regulation of neurofilament proteins and tau in health and disease.Brain research bulletin · 2023Review
- In silico studies on cytotoxicity and antitumoral activity of acetogenins fromFrontiers in chemistry · 2023Article
- The Role of Post-Translational Modifications on the Structure and Function of Tau Protein.Journal of molecular neuroscience : MN · 2022Review
- Dysregulated coordination of MAPT exon 2 and exon 10 splicing underlies different tau pathologies in PSP and AD.Acta neuropathologica · 2022Article
- Does the Anti-Tau Strategy in Progressive Supranuclear Palsy Need to Be Reconsidered? No.Movement disorders clinical practice · 2021Article
- Microglia in Alzheimer's Disease in the Context of Tau Pathology.Biomolecules · 2020Review
- Associations of mitochondrial genomic variation with corticobasal degeneration, progressive supranuclear palsy, and neuropathological tau measures.Acta neuropathologica communications · 2020Article
- Mitochondria in Alzheimer's disease and their potential role in Alzheimer's proteostasis.Experimental neurology · 2020Review
- Mitochondrial DNA Manipulations Affect Tau Oligomerization.Journal of Alzheimer's disease : JAD · 2020Article
- PERK activation mitigates tau pathologyEMBO molecular medicine · 2017Article
- Tau mis-splicing in the pathogenesis of neurodegenerative disorders.BMB reports · 2016Review
- Tau in physiology and pathology.Nature reviews. Neuroscience · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterised by intracellular aggregation of the microtubule-associated protein tau. The tau protein exists in 6 predominant isoforms. Depending on alternative splicing of exon 10, three of these isoforms have four microtubule-binding repeat domains (4R), whilst the others only have three (3R). In PSP there is an excess of the 4R tau isoforms, which are thought to contribute significantly to the pathological process. The cause of this 4R increase is so far unknown. Several lines of evidence link mitochondrial complex I inhibition to the pathogenesis of PSP. We demonstrate here for the first time that annonacin and MPP(+), two prototypical mitochondrial complex I inhibitors, increase the 4R isoforms of tau in human neurons. We show that the splicing factor SRSF2 is necessary to increase 4R tau with complex I inhibition. We also found SRSF2, as well as another tau splicing factor, TRA2B, to be increased in brains of PSP patients. Thereby, we provide new evidence that mitochondrial complex I inhibition may contribute as an upstream event to the pathogenesis of PSP and suggest that splicing factors may represent an attractive therapeutic target to intervene in the disease process.
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