ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Amyloid beta induces the morphological neurodegenerative triad of spine loss, dendritic simplification, and neuritic dystrophies through calcineurin activation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 251 papers.
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Who cites it
251 citing papers in PubMed, 369 citations in OpenAlex.
- Differential relationships of reactive astrocytes and microglia to fibrillar amyloid deposits in Alzheimer disease.Journal of neuropathology and experimental neurology · 2013Trial
- Clemizole, a TRPC5 channel blocker rescues amyloid-β toxicity and cognitive impairment by modulating mitochondrial dysfunction and memory-related proteins.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Gallein-Loaded Albumin Nanoparticles Prevent Amyloid-β-Induced Amyloidogenic APP Processing, Synaptic Loss, and Dendritic Pathology.Molecular neurobiology · 2026Article
- The role of Annexin A2 in Alzheimer's disease: From cellular functions to therapeutic potential.The FEBS journal · 2026Review
- Decoding shared pathogenic networks of oxidative stress in neuropsychiatric disorders to prioritize multi-target therapeutics from natural products.Cell biology and toxicology · 2026Article
- Long non-coding SINEUP RNA enhancing BDNF translation prevents dendritic atrophy following an Aβ-peptide challenge.Cellular and molecular life sciences : CMLS · 2026Article
- Pre-plaque glutamatergic hyperexcitability, mitochondrial dysfunction, and dendritic remodeling in the hippocampus of one-month-old 5xFAD mice.Frontiers in aging neuroscience · 2026Article
- Soluble high-molecular-weight amyloid-β species derived from amyloid-β-laden brains induce cerebral β-amyloidosis.Brain communications · 2026Article
- Hippocampal volume moderates the association between cerebrospinal fluid growth-associated protein 43 and episodic memory performance in older adults.Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition · 2025Article
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- Inhibition of astrocyte signaling leads to sex-specific changes in microglia phenotypes in a diet-based model of cerebral small vessel disease.Journal of neuroinflammation · 2025Article
- Unveiling the role of Na⁺/K⁺-ATPase pump: neurodegenerative mechanisms and therapeutic horizons.Pharmacological reports : PR · 2025Review
- Calcineurin inhibition may prevent Alzheimer disease in people with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Familial Alzheimer's disease mutations in amyloid precursor protein impair calcineurin signaling to NMDA receptors.The Journal of biological chemistry · 2025Article
- Calcineurin/NFAT inhibitors maintain cognition in a preclinical prevention study in an aging canine model of Alzheimer disease.Neurobiology of aging · 2025Article
- Neuronal and glial dysfunction, white matter hyperintensities and cognition in ageing and Alzheimer's disease.Brain communications · 2025Article
- Neuroprotection against beta-amyloid toxicity by the novel estrogen receptor modulator STX requires convergent signaling pathways.Frontiers in molecular neuroscience · 2025Article
- GAP-43 is associated with faster amyloid-associated neurodegeneration and cognitive decline in Alzheimer's disease.Frontiers in neurology · 2025Article
- Amyloid-β Causes NMDA Receptor Dysfunction and Dendritic Spine Loss through mGluR1 and AKAP150-Anchored Calcineurin Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Hybrid Amyloid Quantum Dot Nano-Bio Assemblies to Probe Neuroinflammatory Damage.ACS chemical neuroscience · 2024Article
191 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Amyloid beta (Abeta)-containing plaques are surrounded by dystrophic neurites in the Alzheimer's disease (AD) brain, but whether and how plaques induce these neuritic abnormalities remain unknown. We tested the hypothesis that soluble oligomeric assemblies of Abeta, which surround plaques, induce calcium-mediated secondary cascades that lead to dystrophic changes in local neurites. We show that soluble Abeta oligomers lead to activation of the calcium-dependent phosphatase calcineurin (CaN) (PP2B), which in turn activates the transcriptional factor nuclear factor of activated T cells (NFAT). Activation of these signaling pathways, even in the absence of Abeta, is sufficient to produce a virtual phenocopy of Abeta-induced dystrophic neurites, dendritic simplification, and dendritic spine loss in both neurons in culture and in the adult mouse brain. Importantly, the morphological deficits in the vicinity of Abeta deposits in a mouse model of AD are ameliorated by CaN inhibition, supporting the hypothesis that CaN-NFAT are aberrantly activated by Abeta and that CaN-NFAT activation is responsible for disruption of neuronal structure near plaques. In accord with this, we also detect increased levels of an active form of CaN and NFATc4 in the nuclear fraction from the cortex of patients with AD. Thus, Abeta appears to mediate the neurodegeneration of AD, at least in part, by activation of CaN and subsequent NFAT-mediated downstream cascades.
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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.