ArticleThe Journal of biological chemistry2013
Isomerase Pin1 stimulates dephosphorylation of tau protein at cyclin-dependent kinase (Cdk5)-dependent Alzheimer phosphorylation sites.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 66 citations in OpenAlex.
- Review
- Mapping Phosphorylation-Specific Pin1-CRMP2 Interactions Using an Integrated Mass Spectrometry Approach.ACS chemical biology · 2026Article
- Visceral adipose tissue differentially affects tau and Aβ pathology in 3xTg-AD mice.Cell communication and signaling : CCS · 2026Article
- Beyond microtubule regulation: the multifaceted roles of tau in neuronal function and dysfunction.Translational psychiatry · 2026Review
- Proline-directed phosphorylation and prolyl isomerization oppose each other to regulate PSD-95 ubiquitination and excitatory synaptic plasticity.Frontiers in molecular neuroscience · 2026Article
- Elevated polyglutamylation and tau phosphorylation levels are associated with cognitive impairment at diagnosis in patients with primary central nervous system lymphoma.Alzheimer's research & therapy · 2025Article
- From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer's Disease Landscape.Medicina (Kaunas, Lithuania) · 2025Review
- Interplay Between Aging and Tau Pathology in Alzheimer's Disease: Mechanisms and Translational Perspectives.Antioxidants (Basel, Switzerland) · 2025Review
- Protein modification in neurodegenerative diseases.MedComm · 2024Review
- G272V and P301L Mutations Induce Isoform Specific Tau Mislocalization to Dendritic Spines and Synaptic Dysfunctions in Cellular Models of 3R and 4R Tau Frontotemporal Dementia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Cognitive integrity in Non-Demented Individuals with Alzheimer's Neuropathology is associated with preservation and remodeling of dendritic spines.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
- The role of the Pin1-Frontiers in cell and developmental biology · 2024Review
- Recent insights from non-mammalian models of brain injuries: an emerging literature.Frontiers in neurology · 2024Review
- An Insight into Cellular and Molecular Mechanisms Underlying the Pathogenesis of Neurodegeneration in Alzheimer's Disease.Biomedicines · 2023Review
- Oxidative Stress in Tauopathies: From Cause to Therapy.Antioxidants (Basel, Switzerland) · 2022Review
- The LPA-CDK5-tau pathway mediates neuronal injury in an in vitro model of ischemia-reperfusion insult.BMC neurology · 2022Article
- Article
- Programmed Cell Death Protein 1 Blockade Reduces Glycogen Synthase Kinase 3β Activity and Tau Hyperphosphorylation in Alzheimer's Disease Mouse Models.Frontiers in cell and developmental biology · 2021Article
- Biochemical Markers in Alzheimer's Disease.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurodegenerative diseases associated with the pathological aggregation of microtubule-associated protein Tau are classified as tauopathies. Alzheimer disease, the most common tauopathy, is characterized by neurofibrillary tangles that are mainly composed of abnormally phosphorylated Tau. Similar hyperphosphorylated Tau lesions are found in patients with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) that is induced by mutations within the tau gene. To further understand the etiology of tauopathies, it will be important to elucidate the mechanism underlying Tau hyperphosphorylation. Tau phosphorylation occurs mainly at proline-directed Ser/Thr sites, which are targeted by protein kinases such as GSK3β and Cdk5. We reported previously that dephosphorylation of Tau at Cdk5-mediated sites was enhanced by Pin1, a peptidyl-prolyl isomerase that stimulates dephosphorylation at proline-directed sites by protein phosphatase 2A. Pin1 deficiency is suggested to cause Tau hyperphosphorylation in Alzheimer disease. Up to the present, Pin1 binding was only shown for two Tau phosphorylation sites (Thr-212 and Thr-231) despite the presence of many more hyperphosphorylated sites. Here, we analyzed the interaction of Pin1 with Tau phosphorylated by Cdk5-p25 using a GST pulldown assay and Biacore approach. We found that Pin1 binds and stimulates dephosphorylation of Tau at all Cdk5-mediated sites (Ser-202, Thr-205, Ser-235, and Ser-404). Furthermore, FTDP-17 mutant Tau (P301L or R406W) showed slightly weaker Pin1 binding than non-mutated Tau, suggesting that FTDP-17 mutations induce hyperphosphorylation by reducing the interaction between Pin1 and Tau. Together, these results indicate that Pin1 is generally involved in the regulation of Tau hyperphosphorylation and hence the etiology of tauopathies.
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