ArticleJournal of Alzheimer's disease : JAD2019
Alzheimer's Disease Presenilin-1 Mutation Sensitizes Neurons to Impaired Autophagy Flux and Propofol Neurotoxicity: Role of Calcium Dysregulation.
Article in Journal of Alzheimer's disease : JAD, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- The dual role of glycogen synthase kinase-3 beta (GSK3β) in neurodegenerative pathologies: interplay between autophagy and disease progression.Frontiers in pharmacology · 2025Review
- Pathophysiologic abnormalities in transgenic mice carrying the Alzheimer disease PSEN1 Δ440 mutation.Human molecular genetics · 2024Article
- Mechanisms of autophagy-lysosome dysfunction in neurodegenerative diseases.Nature reviews. Molecular cell biology · 2024Review
- Article
- Tau protein plays a role in the mechanism of cognitive disorders induced by anesthetic drugs.Frontiers in neuroscience · 2023Review
- Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease.Frontiers in aging neuroscience · 2023Review
- Crucial role of autophagy in propofol-treated neurological diseases: a comprehensive review.Frontiers in cellular neuroscience · 2023Review
- Article
- Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene.International journal of molecular sciences · 2022Review
- Potential mechanisms underlying lithium treatment for Alzheimer's disease and COVID-19.European review for medical and pharmacological sciences · 2022Review
- MicroRNA-17-5p Protects against Propofol Anesthesia-Induced Neurotoxicity and Autophagy Impairment via Targeting BCL2L11.Computational and mathematical methods in medicine · 2022Article
- Ryanodine Receptors: A Potential Treatment Target in Various Neurodegenerative Disease.Cellular and molecular neurobiology · 2021Review
- Goldilocks and propofol dosage in older adults: Too much, too little, or just right?Journal of the American Geriatrics Society · 2021Article
- Elevating the Levels of Calcium Ions Exacerbate Alzheimer's Disease via Inducing the Production and Aggregation of β-Amyloid Protein and Phosphorylated Tau.International journal of molecular sciences · 2021Review
- Calcium Ions Aggravate Alzheimer's Disease Through the Aberrant Activation of Neuronal Networks, Leading to Synaptic and Cognitive Deficits.Frontiers in molecular neuroscience · 2021Review
- Sevoflurane modulates breast cancer cell survival via modulation of intracellular calcium homeostasis.BMC anesthesiology · 2020Article
- [Progress on loss-of-function hypothesis of presenilin-1 mutations in Alzheimer diseases].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2020Article
- Up-regulation of miR-137 can inhibit PTN in target manner to regulate PTN/PTPRZ pathway to prevent cognitive dysfunction caused by propofol.American journal of translational research · 2020Article
- Intranasal Dantrolene as a Disease-Modifying Drug in Alzheimer 5XFAD Mice.Journal of Alzheimer's disease : JAD · 2020Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundDisruption of intracellular Ca2+ homeostasis and associated autophagy dysfunction contribute to neuropathology in Alzheimer's disease (AD).
objectiveTo study the effects of propofol on cell viability via its effects on intracellular Ca2+ homeostasis, and the impact of autophagy, in a neuronal model of presenilin-mutated familial AD (FAD).
methodsWe treated PC12 cells, stably transfected with either mutated presenilin-1 (L286V) or wild type (WT) controls, with propofol at different doses and durations, in the presence or absence of extracellular Ca2+, antagonists of inositol trisphosphate receptors (InsP3R, xestospongin C) and/or ryanodine receptors (RYR, dantrolene), or an inhibitor of autophagy flux (Bafilomycin). We determined cell viability, cytosolic Ca2+ concentrations ([Ca2+]c), vATPase protein expression, and lysosomal acidification.
resultsThe propofol dose- and time-dependently decreased cell viability significantly more in L286V than WT cells, especially at the pharmacological dose (>50μM), and together with bafilomycin (40 nM). Clinically used concentrations of propofol (<20μM) tended to increase cell viability. Propofol significantly increased [Ca2+]c more in L286V than in WT cells, which was associated with decrease of vATPase expression and localization to the lysosome. Both toxicity and increased Ca2+ levels were ameliorated by inhibiting InsP3R/RYR. However, the combined inhibition of both receptors paradoxically increased [Ca2+]c, by inducing Ca2+ influx from the extracellular space, causing greater cytotoxicity.
conclusionImpairment in autophagy function acts to deteriorate cell death induced by propofol in FAD neuronal cells. Cell death is ameliorated by either RYR or InsP3R antagonists on their own, but not when both are co-administered.
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