ArticleScience translational medicine2021
PAC1 receptor-mediated clearance of tau in postsynaptic compartments attenuates tau pathology in mouse brain.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Sustained hyperactivity of parasubthalamic nucleus by PACAP signaling mediates stress-induced anxiety.Molecular psychiatry · 2026Article
- Articular cartilage thickness alterations in hind limb of young and aged PAC1 gene-deficient mice.Cell and tissue research · 2026Article
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Early proteasome downregulation and dysfunction drive proteostasis failure in Alzheimer's disease.Brain : a journal of neurology · 2025Article
- More Than Three Decades After Discovery of the Neuroprotective Effect of PACAP, What Is Still Preventing Its Clinical Use?Journal of molecular neuroscience : MN · 2025Review
- mGluR5 in Pyramidal Neurons in the Hippocampus Mediates Chronic Stress-Induced Memory Deficits.CNS neuroscience & therapeutics · 2025Article
- Activation of central Angiotensin-(1-7)/Mas receptor alleviates synaptic damage in diabetes-associated cognitive impairment via modulating AKT/FOXO1/PACAP axis.International journal of biological sciences · 2025Article
- 9-Methylfascaplysin Prevents Neuroinflammation and Synaptic Damage via Cell-Specific Inhibition of Kinases in APP/PS1 Transgenic Mice.CNS neuroscience & therapeutics · 2024Article
- Tau here, tau there, tau almost everywhere: Clarifying the distribution of tau in the adult CNS.Cytoskeleton (Hoboken, N.J.) · 2024Article
- Synaptic alterations associated with disrupted sensory encoding in a mouse model of tauopathy.Brain communications · 2024Article
- 5-HT4 receptor agonists treatment reduces tau pathology and behavioral deficit in the PS19 mouse model of tauopathy.Frontiers in cellular neuroscience · 2024Article
- Synaptic proteasome is inhibited in Alzheimer's disease models and associates with memory impairment in mice.Communications biology · 2023Article
- Multivalent Tau/PSD-95 interactions arrest in vitro condensates and clusters mimicking the postsynaptic density.Nature communications · 2023Article
- PACAP-Sirtuin3 alleviates cognitive impairment through autophagy in Alzheimer's disease.Alzheimer's research & therapy · 2023Article
- Serum tau protein elevation in migraine: a cross-sectional case-control study.The journal of headache and pain · 2023Article
- Disrupting pathologic phase transitions in neurodegeneration.The Journal of clinical investigation · 2023Review
- OMICS Analyses Unraveling Related Gene and Protein-Driven Molecular Mechanisms Underlying PACAP 38-Induced Neurite Outgrowth in PC12 Cells.International journal of molecular sciences · 2023Article
- Accumulation of pTau231 at the Postsynaptic Density in Early Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Article
- Alzheimer's disease as a synaptopathy: Evidence for dysfunction of synapses during disease progression.Frontiers in synaptic neuroscience · 2023Review
- Targeting VIP and PACAP Receptor Signaling: New Insights into Designing Drugs for the PACAP Subfamily of Receptors.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Accumulation of pathological tau in synapses has been identified as an early event in Alzheimer's disease (AD) and correlates with cognitive decline in patients with AD. Tau is a cytosolic axonal protein, but under disease conditions, tau accumulates in postsynaptic compartments and presynaptic terminals, due to missorting within neurons, transsynaptic transfer between neurons, or a failure of clearance pathways. Using subcellular fractionation of brain tissue from rTg4510 tau transgenic mice with tauopathy and human postmortem brain tissue from patients with AD, we found accumulation of seed-competent tau predominantly in postsynaptic compartments. Tau-mediated toxicity in postsynaptic compartments was exacerbated by impaired proteasome activity detected by measuring lysine-48 polyubiquitination of proteins targeted for proteasomal degradation. To combat the accumulation of tau and proteasome impairment in the postsynaptic compartments of rTg4510 mouse brain, we stimulated the pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1R) with its ligand PACAP administered intracerebroventricularly to rTg4510 mice. We observed enhanced synaptic proteasome activity and reduced total tau in postsynaptic compartments in mouse brain after PACAP treatment. The clearance of tau from postsynaptic compartments correlated with attenuated tauopathy and improved cognitive performance of rTg4510 transgenic mice on two behavioral tests. These results suggest that activating PAC1R could prevent accumulation of aggregate-prone tau and indicate a potential therapeutic approach for AD and other tauopathies.
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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.