ArticleThe Journal of experimental medicine2018
Delta-secretase (AEP) mediates tau-splicing imbalance and accelerates cognitive decline in tauopathies.
Article in The Journal of experimental medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Pooled it
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Phosphorylation of YBX1 in the Kidneys is Altered in Legumain Knockout-Mice.Journal of proteome research · 2026Article
- Expression Patterns of T-Cell Intracellular Antigen 1 in Neurodegenerative Disorders and Stroke.International journal of molecular sciences · 2026Review
- Roles of C/EBPβ/AEP in Neurodegenerative Diseases.Current topics in medicinal chemistry · 2025Review
- Complicated Role of Post-translational Modification and Protease-Cleaved Fragments of Tau in Alzheimer's Disease and Other Tauopathies.Molecular neurobiology · 2024Review
- Oligomeric, phosphorylated, and truncated tau and spliceosome pathology within the entorhinal-hippocampal connectome across stages of Alzheimer's disease.The Journal of comparative neurology · 2023Article
- eQTL colocalization analysis highlights novel susceptibility genes in Autism Spectrum Disorders (ASD).Translational psychiatry · 2023Article
- Bacteroides Fragilis in the gut microbiomes of Alzheimer's disease activates microglia and triggers pathogenesis in neuronal C/EBPβ transgenic mice.Nature communications · 2023Article
- The Role of Tau Proteoforms in Health and Disease.Molecular neurobiology · 2023Review
- Development of an α-synuclein positron emission tomography tracer for imaging synucleinopathies.Cell · 2023Article
- C/EBPβ/AEP Signaling Drives Alzheimer's Disease Pathogenesis.Neuroscience bulletin · 2023Review
- The Mammalian Cysteine Protease Legumain in Health and Disease.International journal of molecular sciences · 2022Review
- The emerging role of autophagy and mitophagy in tauopathies: From pathogenesis to translational implications in Alzheimer's disease.Frontiers in aging neuroscience · 2022Review
- ApoE4 activates C/EBPβ/δ-secretase with 27-hydroxycholesterol, driving the pathogenesis of Alzheimer's disease.Progress in neurobiology · 2021Article
- Metabolic disorder in Alzheimer's disease.Metabolic brain disease · 2021Review
- The Mechanism of Asparagine Endopeptidase in the Progression of Malignant Tumors: A Review.Cells · 2021Review
- Stress Granules and Neurodegenerative Disorders: A Scoping Review.Frontiers in aging neuroscience · 2021Article
- Article
- Delta-secretase cleavage of Tau mediates its pathology and propagation in Alzheimer's disease.Experimental & molecular medicine · 2020Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
SRPK2 is abnormally activated in tauopathies including Alzheimer's disease (AD). SRPK2 is known to play an important role in pre-mRNA splicing by phosphorylating SR-splicing factors. Dysregulation of tau exon 10 pre-mRNA splicing causes pathological imbalances in 3R- and 4R-tau, leading to neurodegeneration; however, the role of SRPK2 in these processes remains unclear. Here we show that delta-secretase (also known as asparagine endopeptidase; AEP), which is activated in AD, cleaves SRPK2 and increases its nuclear translocation as well as kinase activity, augmenting exon 10 inclusion. Conversely, AEP-uncleavable SRPK2 N342A mutant increases exon 10 exclusion. Lentiviral expression of truncated SRPK2 increases 4R-tau isoforms and accelerates cognitive decline in htau mice. Uncleavable SRPK2 N342A expression improves synaptic functions and prevents spatial memory deficits in tau intronic mutant FTDP-17 transgenic mice. Hence, AEP mediates tau-splicing imbalance in tauopathies via cleaving SRPK2.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.