ArticleCell death discovery2015
WWOX dysfunction induces sequential aggregation of TRAPPC6AΔ, TIAF1, tau and amyloid β, and causes apoptosis.
Article in Cell death discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.Nature genetics · 2019Pooled it
- Neuron-specific WWOX gene therapy produces dose-dependent, durable rescue in a model of WWOX-related epileptic encephalopathy.Molecular therapy. Advances · 2026Article
- Single-cell spatial map of cis-regulatory elements for disease-related genes in the macaque cortex.Nature communications · 2026Article
- TRAPPopathies: Severe Multisystem Disorders Caused by Variants in Genes of the Transport Protein Particle (TRAPP) Complexes.International journal of molecular sciences · 2024Review
- Dissociation of the nuclear WWOX/TRAF2 switch renders UV/cold shock-mediated nuclear bubbling cell death at low temperatures.Cell communication and signaling : CCS · 2024Article
- Zfra Overrides WWOX in Suppressing the Progression of Neurodegeneration.International journal of molecular sciences · 2024Review
- Article
- Biochemical Structure and Function of TRAPP Complexes in the Cardiac System.JACC. Basic to translational science · 2023Article
- Plasma biomarkers and genetics in the diagnosis and prediction of Alzheimer's disease.Brain : a journal of neurology · 2023Article
- Zfra Inhibits the TRAPPC6AΔ-Initiated Pathway of Neurodegeneration.International journal of molecular sciences · 2022Article
- Review
- Astrocytes in Neurodegenerative Diseases: A Perspective from Tauopathy and α-Synucleinopathy.Life (Basel, Switzerland) · 2021Review
- Review
- Cell-type-specific expression quantitative trait loci associated with Alzheimer disease in blood and brain tissue.Translational psychiatry · 2021Article
- Neurological Disorders Associated with WWOX Germline Mutations-A Comprehensive Overview.Cells · 2021Review
- Fragile GeneFrontiers in oncology · 2021Article
- Systematic analysis of expression signatures of neuronal subpopulations in the VTA.Molecular brain · 2019Article
- A p53/TIAF1/WWOX triad exerts cancer suppression but may cause brain protein aggregation due to p53/WWOX functional antagonism.Cell communication and signaling : CCS · 2019Article
- Chasing the signaling run by tri-molecular time-lapse FRET microscopy.Cell death discovery · 2018Article
- WWOX Phosphorylation, Signaling, and Role in Neurodegeneration.Frontiers in neuroscience · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Aggregated vesicle-trafficking protein isoform TRAPPC6AΔ (TPC6AΔ) has a critical role in causing caspase activation, tau aggregation and Aβ generation in the brains of nondemented middle-aged humans, patients with Alzheimer's disease (AD) and 3-week-old Wwox gene knockout mice. WWOX blocks neurodegeneration via interactions with tau and tau-phosphorylating enzymes. WWOX deficiency leads to epilepsy, mental retardation and early death. Here, we demonstrated that TGF-β1 induces shuttling of endogenous wild-type TPC6A and TPC6AΔ in between nucleoli and mitochondria (~40-60 min per round trip), and WWOX reduces the shuttling time by 50%. TGF-β1 initially maximizes the binding of TPC6AΔ to the C-terminal tail of WWOX, followed by dissociation. TPC6AΔ then undergoes aggregation, together with TIAF1 (TGF-β1-induced antiapoptotic factor), in the mitochondria to induce apoptosis. An additional rescue scenario is that TGF-β1 induces Tyr33 phosphorylation and unfolding of WWOX and its the N-terminal WW domain slowly binds TPC6AΔ to block aggregation and apoptosis. Similarly, loss of WWOX induces TPC6AΔ polymerization first, then aggregation of TIAF1, amyloid β and tau, and subsequent cell death, suggesting that a cascade of protein aggregation leads to neurodegeneration.
Identifiers
What OpenQuestion holds
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.