ArticleScientific reports2016
Accumulation of human full-length tau induces degradation of nicotinic acetylcholine receptor α4 via activating calpain-2.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
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- Seeding Alzheimer's disease-associated tau pathology in MAPT knock-in primary neurons causes early axonopathy and synaptic dysfunction.Scientific reports · 2025Article
- Pathological and Functional Brain Amyloids: A New Concept Explaining the Differences.International journal of molecular sciences · 2025Review
- Peroxiredoxin 1 inhibits streptozotocin-induced Alzheimer's disease-like pathology in hippocampal neuronal cells via the blocking of CaScientific reports · 2024Article
- Hippocampal mitochondrial CaSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Article
- Regulation of Neurodegeneration-associated Protein Fragments by the N-degron Pathways.Neurotoxicity research · 2022Review
- Pursuing High-Resolution Structures of Nicotinic Acetylcholine Receptors: Lessons Learned from Five Decades.Molecules (Basel, Switzerland) · 2021Review
- Amelioration of oxidative stress and neuroinflammation in lipopolysaccharide-induced memory impairment using Rosmarinic acid in mice.Metabolic brain disease · 2021Article
- Human Tau Isoforms and Proteolysis for Production of Toxic Tau Fragments in Neurodegeneration.Frontiers in neuroscience · 2021Review
- Possible Mechanisms of Tau Spread and Toxicity in Alzheimer's Disease.Frontiers in cell and developmental biology · 2021Review
- Tau-induced upregulation of C/EBPβ-TRPC1-SOCE signaling aggravates tauopathies: A vicious cycle in Alzheimer neurodegeneration.Aging cell · 2020Article
- Tau and Alpha Synuclein Synergistic Effect in Neurodegenerative Diseases: When the Periphery Is the Core.International journal of molecular sciences · 2020Review
- Involvement of calpain in the neuropathogenesis of Alzheimer's disease.Medicinal research reviews · 2019Review
- Gene Profiling of Nucleus Basalis Tau Containing Neurons in Chronic Traumatic Encephalopathy: A Chronic Effects of Neurotrauma Consortium Study.Journal of neurotrauma · 2018Article
- Cognitive correlates of α4β2 nicotinic acetylcholine receptors in mild Alzheimer's dementia.Brain : a journal of neurology · 2018Article
- Protection against TBI-Induced Neuronal Death with Post-Treatment with a Selective Calpain-2 Inhibitor in Mice.Journal of neurotrauma · 2018Article
- Calpain-2 as a therapeutic target for acute neuronal injury.Expert opinion on therapeutic targets · 2018Review
- Nature of Tau-Associated Neurodegeneration and the Molecular Mechanisms.Journal of Alzheimer's disease : JAD · 2018Review
- Tau Proteolysis in the Pathogenesis of Tauopathies: Neurotoxic Fragments and Novel Biomarkers.Journal of Alzheimer's disease : JAD · 2018Review
- M-Calpain Activation Facilitates Seizure Induced KCC2 Down Regulation.Frontiers in molecular neuroscience · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholinergic impairments and tau accumulation are hallmark pathologies in sporadic Alzheimer's disease (AD), however, the intrinsic link between tau accumulation and cholinergic deficits is missing. Here, we found that overexpression of human wild-type full-length tau (termed hTau) induced a significant reduction of α4 subunit of nicotinic acetylcholine receptors (nAChRs) with an increased cleavage of the receptor producing a ~55kDa fragment in primary hippocampal neurons and in the rat brains, meanwhile, the α4 nAChR currents decreased. Further studies demonstrated that calpains, including calpain-1 and calpain-2, were remarkably activated with no change of caspase-3, while simultaneous suppression of calpain-2 by selective calpain-2 inhibitor but not calpain-1 attenuated the hTau-induced degradation of α4 nAChR. Finally, we demonstrated that hTau accumulation increased the basal intracellular calcium level in primary hippocampal neurons. We conclude that the hTau accumulation inhibits nAChRs α4 by activating calpain-2. To our best knowledge, this is the first evidence showing that the intracellular accumulation of tau causes cholinergic impairments.
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