ArticleFrontiers in synaptic neuroscience2011
Blocking Effects of Human Tau on Squid Giant Synapse Transmission and Its Prevention by T-817 MA.
Article in Frontiers in synaptic neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- The PANoptosis-related hippocampal molecular subtypes and key biomarkers in Alzheimer's disease patients.Scientific reports · 2024Article
- Calcineurin inhibition prevents synaptic plasticity deficit induced by brain-derived tau oligomers.Brain communications · 2024Article
- Hyperphosphorylated tau (p-tau) and drug discovery in the context of Alzheimer's disease and related tauopathies.Drug discovery today · 2023Review
- Alzheimer's disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression.Frontiers in synaptic neuroscience · 2023Review
- Role of Aβ in Alzheimer's-related synaptic dysfunction.Frontiers in cell and developmental biology · 2022Review
- Amyloid Prefibrillar Oligomers: The Surprising Commonalities in Their Structure and Activity.International journal of molecular sciences · 2021Review
- Development of novel phosphodiesterase 5 inhibitors for the therapy of Alzheimer's disease.Biochemical pharmacology · 2020Review
- Axonal Degeneration in AD: The Contribution of Aβ and Tau.Frontiers in aging neuroscience · 2020Review
- AD-Related N-Terminal Truncated Tau Is Sufficient to Recapitulate In Vivo the Early Perturbations of Human Neuropathology: Implications for Immunotherapy.Molecular neurobiology · 2018Article
- The Neurotoxic Role of Extracellular Tau Protein.International journal of molecular sciences · 2018Review
- Extracellular truncated tau causes early presynaptic dysfunction associated with Alzheimer's disease and other tauopathies.Oncotarget · 2017Article
- Tau pathology-mediated presynaptic dysfunction.Neuroscience · 2016Article
- Behind the curtain of tauopathy: a show of multiple players orchestrating tau toxicity.Cellular and molecular life sciences : CMLS · 2016Review
- Mechanism of Oxidative Stress and Synapse Dysfunction in the Pathogenesis of Alzheimer's Disease: Understanding the Therapeutics Strategies.Molecular neurobiology · 2016Review
- Tau Oligomers: The Toxic Player at Synapses in Alzheimer's Disease.Frontiers in cellular neuroscience · 2015Review
- Article
- Review
- Cephalopods in neuroscience: regulations, research and the 3Rs.Invertebrate neuroscience : IN · 2014Review
- Rescue of tau-induced synaptic transmission pathology by paclitaxel.Frontiers in cellular neuroscience · 2014Article
- The involvement of cholinergic neurons in the spreading of tau pathology.Frontiers in neurology · 2013Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Filamentous tau inclusions are hallmarks of Alzheimer's disease and related neurodegenerative tauopathies, but the molecular mechanisms involved in tau-mediated changes in neuronal function and their possible effects on synaptic transmission are unknown. We have evaluated the effects of human tau protein injected directly into the presynaptic terminal axon of the squid giant synapse, which affords functional, structural, and biochemical analysis of its action on the synaptic release process. Indeed, we have found that at physiological concentration recombinant human tau (h-tau42) becomes phosphorylated, produces a rapid synaptic transmission block, and induces the formation of clusters of aggregated synaptic vesicles in the vicinity of the active zone. Presynaptic voltage clamp recordings demonstrate that h-tau42 does not modify the presynaptic calcium current amplitude or kinetics. Analysis of synaptic noise at the post-synaptic axon following presynaptic h-tau42 microinjection revealed an initial phase of increase spontaneous transmitter release followed by a marked reduction in noise. Finally, systemic administration of T-817MA, a proposed neuro-protective agent, rescued tau-induced synaptic abnormalities. Our results show novel mechanisms of h-tau42 mediated synaptic transmission failure and identify a potential therapeutic agent to treat tau-related neurotoxicity.
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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.