ArticleProceedings of the National Academy of Sciences of the United States of America2019
Delta-secretase-cleaved Tau antagonizes TrkB neurotrophic signalings, mediating Alzheimer's disease pathologies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Amyloid beta levels and occludin depletion in low dose heavy metal mixture mediated cerebellar toxicity in Wistar rats.Scientific reports · 2026Article
- Positional scanning and computational modeling reveal determinants of legumain transpeptidase activity.Protein science : a publication of the Protein Society · 2026Article
- Neurotrophins and Galectin-3: Hidden Keys in Neuroinflammation-A Narrative Review.International journal of molecular sciences · 2026Review
- BIN1 Interacts with Tau Fragments to Inhibit TrkB Signaling Endosome Recycling in a Mouse Model of Alzheimer's Disease.Neuroscience bulletin · 2026Article
- Disruption of BDNF signalling in neuropathologies.Biochemical Society transactions · 2026Review
- Immunotherapy against tau fragment diminishes AD pathology, improving synaptic function and cognition.Molecular neurodegeneration · 2025Article
- Harnessing BDNF Signaling to Promote Resilience in Aging.Aging and disease · 2024Review
- BDNF Val66Met moderates episodic memory decline and tau biomarker increases in early sporadic Alzheimer's disease.Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists · 2024Article
- A Combined Computational and Experimental Approach to Studying Tropomyosin Kinase Receptor B Binders for Potential Treatment of Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2024Article
- Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.Signal transduction and targeted therapy · 2024Review
- Targeting brain-derived neurotrophic factor in the treatment of neurodegenerative diseases: A review.Neuroprotection (Chichester, England) · 2024Review
- STAT3 ameliorates truncated tau-induced cognitive deficits.Neural regeneration research · 2024Article
- Inhibition of asparagine endopeptidase (AEP) effectively treats sporadic Alzheimer's disease in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Psilocybin for the treatment of Alzheimer's disease.Frontiers in neuroscience · 2024Review
- TrkB inhibition of DJ-1 degradation promotes the growth and maintenance of cancer stem cell characteristics in hepatocellular carcinoma.Cellular and molecular life sciences : CMLS · 2023Article
- C/EBPβ/AEP Signaling Drives Alzheimer's Disease Pathogenesis.Neuroscience bulletin · 2023Review
- Legumain Functions as a Transient TrkB Sheddase.International journal of molecular sciences · 2023Article
- A tau fragment links depressive-like behaviors and cognitive declines in Alzheimer's disease mouse models through attenuating mitochondrial function.Frontiers in aging neuroscience · 2023Article
- Receptor-Independent Anti-Ferroptotic Activity of TrkB Modulators.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
BDNF, an essential trophic factor implicated in synaptic plasticity and neuronal survival, is reduced in Alzheimer's disease (AD). BDNF deficiency's association with Tau pathology in AD is well documented. However, the molecular mechanisms accounting for these events remain incompletely understood. Here we show that BDNF deprivation triggers Tau proteolytic cleavage by activating δ-secretase [i.e., asparagine endopeptidase (AEP)], and the resultant Tau N368 fragment binds TrkB receptors and blocks its neurotrophic signals, inducing neuronal cell death. Knockout of BDNF or TrkB receptors provokes δ-secretase activation via reducing T322 phosphorylation by Akt and subsequent Tau N368 cleavage, inducing AD-like pathology and cognitive dysfunction, which can be restored by expression of uncleavable Tau N255A/N368A mutant. Blocking the Tau N368-TrkB complex using Tau repeat-domain 1 peptide reverses this pathology. Thus, our findings support that BDNF reduction mediates Tau pathology via activating δ-secretase in AD.
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Registered trials
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