ArticleActa neuropathologica communications2020
Tau-tubulin kinase 1 and amyloid-β peptide induce phosphorylation of collapsin response mediator protein-2 and enhance neurite degeneration in Alzheimer disease mouse models.
Article in Acta neuropathologica communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Orthogonal Ionic Liquid-Based Extraction Strategy Enables Amyloid-Specific Profiling of Aggregate Proteome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Protein kinases as therapeutic targets in Alzheimer's disease: challenges, insights, and new frontiers.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Antisense oligonucleotide-based targeting of Tau-tubulin kinase 1 prevents hippocampal accumulation of phosphorylated tau in PS19 tauopathy mice.Acta neuropathologica communications · 2023Article
- Effect of lidocaine on cognitively impaired rats: Anti-inflammatory and antioxidant mechanisms in combination with CRMP2 antiphosphorylation.Immunity, inflammation and disease · 2023Article
- Tau tubulin kinase 1 and 2 regulate ciliogenesis and human pluripotent stem cells-derived neural rosettes.Scientific reports · 2023Article
- Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis.Scientific reports · 2023Article
- Protein Interactome of Amyloid-β as a Therapeutic Target.Pharmaceuticals (Basel, Switzerland) · 2023Review
- KSFinder-a knowledge graph model for link prediction of novel phosphorylated substrates of kinases.PeerJ · 2023Article
- Multi-omic profiling reveals the ataxia protein sacsin is required for integrin trafficking and synaptic organization.Cell reports · 2022Article
- Treadmill Exercise Reduces Neuroinflammation, Glial Cell Activation and Improves Synaptic Transmission in the Prefrontal Cortex in 3 × Tg-AD Mice.International journal of molecular sciences · 2022Article
- CK2 and protein kinases of the CK1 superfamily as targets for neurodegenerative disorders.Frontiers in molecular biosciences · 2022Review
- Homozygosity Haplotype and Whole-Exome Sequencing Analysis to Identify Potentially Functional Rare Variants Involved in Multiple Sclerosis among Sardinian Families.Current issues in molecular biology · 2021Article
- PKCγ-Mediated Phosphorylation of CRMP2 Regulates Dendritic Outgrowth in Cerebellar Purkinje Cells.Molecular neurobiology · 2020Article
- The Positive Side of the Alzheimer's Disease Amyloid Cross-Interactions: The Case of the Aβ 1-42 Peptide with Tau, TTR, CysC, and ApoA1.Molecules (Basel, Switzerland) · 2020Review
- Axonal Degeneration in AD: The Contribution of Aβ and Tau.Frontiers in aging neuroscience · 2020Review
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6 authors at 2 institutions in 2 countries.
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Abstract
The accumulation of phosphorylated tau protein (pTau) in the entorhinal cortex (EC) is the earliest tau pathology in Alzheimer's disease (AD). Tau tubulin kinase-1 (TTBK1) is a neuron-specific tau kinase and expressed in the EC and hippocampal regions in both human and mouse brains. Here we report that collapsin response mediator protein-2 (CRMP2), a critical mediator of growth cone collapse, is a new downstream target of TTBK1 and is accumulated in the EC region of early stage AD brains. TTBK1 transgenic mice show severe axonal degeneration in the perforant path, which is exacerbated by crossing with Tg2576 mice expressing Swedish familial AD mutant of amyloid precursor protein (APP). TTBK1 mice show accumulation of phosphorylated CRMP2 (pCRMP2), in the EC at 10 months of age, whereas age-matched APP/TTBK1 bigenic mice show pCRMP2 accumulation in both the EC and hippocampal regions. Amyloid-β peptide (Aβ) and TTBK1 suppress the kinetics of microtubule polymerization and TTBK1 reduces the neurite length of primary cultured neurons in Rho kinase-dependent manner in vitro. Silencing of TTBK1 or expression of dominant-negative Rho kinase demonstrates that Aβ induces CRMP2 phosphorylation at threonine 514 in a TTBK1-dependent manner, and TTBK1 enhances Aβ-induced CRMP2 phosphorylation in Rho kinase-dependent manner in vitro. Furthermore, TTBK1 expression induces pCRMP2 complex formation with pTau in vitro, which is enhanced upon Aβ stimulation in vitro. Finally, pCRMP2 forms a complex with pTau in the EC tissue of TTBK1 mice in vivo, which is exacerbated in both the EC and hippocampal tissues in APP/TTBK1 mice. These results suggest that TTBK1 and Aβ induce phosphorylation of CRMP2, which may be causative for the neurite degeneration and somal accumulation of pTau in the EC neurons, indicating critical involvement of TTBK1 and pCRMP2 in the early AD pathology.
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