ArticleMolecular neurodegeneration2019
Synaptic and memory dysfunction induced by tau oligomers is rescued by up-regulation of the nitric oxide cascade.
Article in Molecular neurodegeneration, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 70 citations in OpenAlex.
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- Human iPSC-derived GABAergic interneuron transplantation restores circuit balance and cognitive function in an Alzheimer's disease model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Angiopoietin-2 aggravates Alzheimer's disease by promoting blood-brain barrier dysfunction and neuroinflammation.Cell reports · 2026Article
- Tau oligomers modulate synapse fate by eliciting progressive bipartite synapse dysregulation and synapse loss.Molecular neurodegeneration · 2026Article
- Long-term Locus Coeruleus Stimulation Exacerbates Tau Pathology in PS19 Mice.bioRxiv : the preprint server for biology · 2025Article
- Discovery of Indole-Based PDE5 Inhibitors: Synthesis and Pharmacological Evaluation.ACS medicinal chemistry letters · 2025Article
- Novel strategies for targeting tau oligomers in neurodegenerative diseases.Journal of neurology · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- An Expanded Narrative Review of Neurotransmitters on Alzheimer's Disease: The Role of Therapeutic Interventions on Neurotransmission.Molecular neurobiology · 2025Review
- Oxidative/Nitrosative Stress, Apoptosis, and Redox Signaling: Key Players in Neurodegenerative Diseases.Journal of biochemical and molecular toxicology · 2025Review
- Blockade of dopamine D3 receptors improves hippocampal synaptic function and rescues age-related cognitive phenotype.Aging cell · 2024Article
- The Emerging Role of Phosphodiesterase 5 Inhibition in Neurological Disorders: The State of the Art.Cells · 2024Review
- Deciphering the Role of Peroxisome Proliferator-activated Receptor α and Phosphodiesterase Type 5 Targets in Alzheimer's Disease.CNS & neurological disorders drug targets · 2024Review
- Bioinformatics analyses and experimental validation of ferroptosis-related genes in bronchopulmonary dysplasia pathogenesis.PloS one · 2024Article
- Calcineurin inhibition prevents synaptic plasticity deficit induced by brain-derived tau oligomers.Brain communications · 2024Article
- The 5HT2b Receptor in Alzheimer's Disease: Increased Levels in Patient Brains and Antagonist Attenuation of Amyloid and Tau Induced Dysfunction.Journal of Alzheimer's disease : JAD · 2024Article
- Re-Arranging the Puzzle between the Amyloid-Beta and Tau Pathology: An APP-Centric Approach.International journal of molecular sciences · 2023Review
- Nitric Oxide as a Determinant of Human Longevity and Health Span.International journal of molecular sciences · 2023Review
- Optimizing metabolic stability of phosphodiesterase 5 inhibitors: Discovery of a potent N-(pyridin-3-ylmethyl)quinoline derivative targeting synaptic plasticity.Bioorganic & medicinal chemistry letters · 2023Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundSoluble aggregates of oligomeric forms of tau protein (oTau) have been associated with impairment of synaptic plasticity and memory in Alzheimer's disease. However, the molecular mechanisms underlying the synaptic and memory dysfunction induced by elevation of oTau are still unknown.
methodsThis work used a combination of biochemical, electrophysiological and behavioral techniques. Biochemical methods included analysis of phosphorylation of the cAMP-responsive element binding (CREB) protein, a transcriptional factor involved in memory, histone acetylation, and expression immediate early genes c-Fos and Arc. Electrophysiological methods included assessment of long-term potentiation (LTP), a type of synaptic plasticity thought to underlie memory formation. Behavioral studies investigated both short-term spatial memory and associative memory. These phenomena were examined following oTau elevation.
resultsLevels of phospho-CREB, histone 3 acetylation at lysine 27, and immediate early genes c-Fos and Arc, were found to be reduced after oTau elevation during memory formation. These findings led us to explore whether up-regulation of various components of the nitric oxide (NO) signaling pathway impinging onto CREB is capable of rescuing oTau-induced impairment of plasticity, memory, and CREB phosphorylation. The increase of NO levels protected against oTau-induced impairment of LTP through activation of soluble guanylyl cyclase. Similarly, the elevation of cGMP levels and stimulation of the cGMP-dependent protein kinases (PKG) re-established normal LTP after exposure to oTau. Pharmacological inhibition of cGMP degradation through inhibition of phosphodiesterase 5 (PDE5), rescued oTau-induced LTP reduction. These findings could be extrapolated to memory because PKG activation and PDE5 inhibition rescued oTau-induced memory impairment. Finally, PDE5 inhibition re-established normal elevation of CREB phosphorylation and cGMP levels after memory induction in the presence of oTau.
conclusionsUp-regulation of CREB activation through agents acting on the NO cascade might be beneficial against tau-induced synaptic and memory dysfunctions.
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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.