ArticleScientific reports2017
The tyrosine phosphatase PTPN13/FAP-1 links calpain-2, TBI and tau tyrosine phosphorylation.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Abl kinase activation promotes axon initial segment disassembly and protein sorting defects in Alzheimer's disease.BMC biology · 2026Article
- Differential downstream signaling in microglia lacking Alzheimer's-related TREM2 or its adaptor TYROBP/DAP12.Molecular neurodegeneration advances · 2026Article
- Review
- Review
- An overview of preclinical models of traumatic brain injury (TBI): relevance to pathophysiological mechanisms.Frontiers in cellular neuroscience · 2024Review
- Role of Non-Receptor-Type Tyrosine Phosphatases in Brain-Related Diseases.Molecular neurobiology · 2023Review
- Scientific rationale for the use of α2A-adrenoceptor agonists in treating neuroinflammatory cognitive disorders.Molecular psychiatry · 2023Review
- Single-nucleus RNA-sequencing of autosomal dominant Alzheimer disease and risk variant carriers.Nature communications · 2023Article
- Increased Risk of Aging-Related Neurodegenerative Disease after Traumatic Brain Injury.Biomedicines · 2023Review
- Molecular Tweezers: Supramolecular Hosts with Broad-Spectrum Biological Applications.Pharmacological reviews · 2023Review
- Hereditable variants of classical protein tyrosine phosphatase genes: Will they prove innocent or guilty?Frontiers in cell and developmental biology · 2022Review
- Cleavage and activation of LIM kinase 1 as a novel mechanism for calpain 2-mediated regulation of nuclear dynamics.Scientific reports · 2021Article
- An update on the association between traumatic brain injury and Alzheimer's disease: Focus on Tau pathology and synaptic dysfunction.Neuroscience and biobehavioral reviews · 2021Review
- Calpain-1 and Calpain-2 in the Brain: New Evidence for a Critical Role of Calpain-2 in Neuronal Death.Cells · 2020Review
- Dual Role of the PTPN13 Tyrosine Phosphatase in Cancer.Biomolecules · 2020Review
- Calpain-2 as a therapeutic target in repeated concussion-induced neuropathy and behavioral impairment.Science advances · 2020Article
- Involvement of calpain in the neuropathogenesis of Alzheimer's disease.Medicinal research reviews · 2019Review
- Calpain-1 and Calpain-2 in the Brain: Dr. Jekill and Mr Hyde?Current neuropharmacology · 2019Review
- Tau Pathology in Chronic Traumatic Encephalopathy and Alzheimer's Disease: Similarities and Differences.Frontiers in neurology · 2019Review
- Calpain-2 as a therapeutic target for acute neuronal injury.Expert opinion on therapeutic targets · 2018Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Traumatic brain injury (TBI) increases the risk of Alzheimer's disease (AD). Calpain activation and tau hyperphosphorylation have been implicated in both TBI and AD. However, the link between calpain and tau phosphorylation has not been fully identified. We recently discovered that the two major calpain isoforms in the brain, calpain-1 and calpain-2, play opposite functions in synaptic plasticity and neuronal survival/death, which may be related to their different C-terminal PDZ binding motifs. Here, we identify the tyrosine phosphatase PTPN13 as a key PDZ binding partner of calpain-2. PTPN13 is cleaved by calpain-2, which inactivates its phosphatase activity and generates stable breakdown products (P13BPs). We also found that PTPN13 dephosphorylates and inhibits c-Abl. Following TBI, calpain-2 activation cleaved PTPN13, activated c-Abl and triggered tau tyrosine phosphorylation. The activation of this pathway was responsible for the accumulation of tau oligomers after TBI, as post-TBI injection of a calpain-2 selective inhibitor inhibited c-Abl activation and tau oligomer accumulation. Thus, the calpain-2-PTPN13-c-Abl pathway provides a direct link between calpain-2 activation and abnormal tau aggregation, which may promote tangle formation and accelerate the development of AD pathology after repeated concussions or TBI. This study suggests that P13BPs could be potential biomarkers to diagnose mTBI or AD.
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