ArticlePrion
Cis phosphorylated tau as the earliest detectable pathogenic conformation in Alzheimer disease, offering novel diagnostic and therapeutic strategies.
Article in Prion. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Review
- Cross-Talk Between Tau O-GlcNAcylation and the Formation of the Early Driver of Neurodegeneration (Cis P-Thr231-Pro Tau) in Primary Cortical Neurons.Molecular neurobiology · 2025Article
- A Novel Phosphorylated Tau Conformer Implicated in the Tauopathy Pathogenesis of Human Neurons.Biomolecules · 2025Article
- Review
- Conserved region of human TDP-43 is structurally similar to membrane binding protein FARP1 and protein chaperons BAG6 and CYP33.microPublication biology · 2024Article
- Monoclonal Antibody Therapy in Alzheimer's Disease.Pharmaceutics · 2023Review
- Long-term normalization of calcineurin activity in model mice rescues Pin1 and attenuates Alzheimer's phenotypes without blocking peripheral T cell IL-2 response.Alzheimer's research & therapy · 2023Article
- Application of Pt@ZIF-8 nanocomposite-based electrochemical biosensor for sensitive diagnosis of tau protein in Alzheimer's disease patients.Scientific reports · 2023Article
- The propagation mechanisms of extracellular tau in Alzheimer's disease.Journal of neurology · 2022Review
- Tau Pathology Triggered by Spinal Cord Injury Can Play a Critical Role in the Neurotrauma Development.Molecular neurobiology · 2020Review
- Advances and considerations in AD tau-targeted immunotherapy.Neurobiology of disease · 2020Review
- Phosphorylation-Dependent Pin1 Isomerization of ATR: Its Role in Regulating ATR's Anti-apoptotic Function at Mitochondria, and the Implications in Cancer.Frontiers in cell and developmental biology · 2020Review
- It's all about tau.Progress in neurobiology · 2019Review
- Nuclear Tau, p53 and Pin1 Regulate PARN-Mediated Deadenylation and Gene Expression.Frontiers in molecular neuroscience · 2019Article
- Death-Associated Protein Kinase 1 as a Promising Drug Target in Cancer and Alzheimer's Disease.Recent patents on anti-cancer drug discovery · 2019Review
- Therapeutic implications of how TNF links apolipoprotein E, phosphorylated tau, α-synuclein, amyloid-β and insulin resistance in neurodegenerative diseases.British journal of pharmacology · 2018Review
- "Tau immunotherapy: Hopes and hindrances".Human vaccines & immunotherapeutics · 2018Article
- Pathologic ThrNeurology · 2018Article
- Targeting Prion-like Cis Phosphorylated Tau Pathology in Neurodegenerative Diseases.Journal of Alzheimer's disease & Parkinsonism · 2018Article
- Chronic Repetitive Mild Traumatic Brain Injury Results in Reduced Cerebral Blood Flow, Axonal Injury, Gliosis, and Increased T-Tau and Tau Oligomers.Journal of neuropathology and experimental neurology · 2016Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
After protein phosphorylation on certain serine or threonine residues preceding a proline (pSer/Thr-Pro), the function of certain phosphorylated protein is further regulated by cis-trans conformational change. Due to the lack of any tool to detect such two conformations in cells, however, it is not even known whether any cis or trans conformation exists in vivo, not to mention their conformation-specific functions or regulation. We developed a novel peptide chemistry technology to generate the first pair of antibodies that can distinguish cis from trans pThr231-Pro tau. Cis, but not trans, pThr231-tau appears early in mild cognitive impairment (MCI) neurons and further accumulates in only degenerating neurons as Alzheimer disease (AD) progresses, localizing to dystrophic neurites, which are known to correlate well with memory loss. Unlike trans p-tau, the cis cannot promote microtubule assembly, and is more resistant to dephosphorylation and degradation and more prone to aggregation. Pin1 accelerates cis to trans isomerization to prevent tau pathology in AD. Thus, during MCI and AD development, cis pThr231-Pro tau is the earliest detectable pathogenic tau conformation and antibodies and vaccines against the pathogenic cis p-tau may be used for the early diagnosis and treatment of AD. These findings offer in vivo approach to study conformational regulation of Pro-directed phosphorylation signaling.
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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.