ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience1998
Increased sensitivity to mitochondrial toxin-induced apoptosis in neural cells expressing mutant presenilin-1 is linked to perturbed calcium homeostasis and enhanced oxyradical production.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
53 citing papers in PubMed, 216 citations in OpenAlex.
- Stress survival and longevity ofToxicology research · 2024Article
- Research Progress on the Pathogenesis, Diagnosis, and Drug Therapy of Alzheimer's Disease.Brain sciences · 2024Review
- Review
- Presenilin: A Multi-Functional Molecule in the Pathogenesis of Alzheimer's Disease and Other Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Mitochondrial dynamics in health and disease: mechanisms and potential targets.Signal transduction and targeted therapy · 2023Review
- Potential mechanisms underlying lithium treatment for Alzheimer's disease and COVID-19.European review for medical and pharmacological sciences · 2022Review
- Clinical relevance of biomarkers, new therapeutic approaches, and role of post-translational modifications in the pathogenesis of Alzheimer's disease.Frontiers in aging neuroscience · 2022Review
- The Effect of NeuroAid (MLC901) on Cholestasis-Induced Spatial Memory Impairment with Respect to the Expression of BAX, BCL-2, BAD, PGC-1α and TFAM Genes in the Hippocampus of Male Wistar Rats.Neurochemical research · 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
- Article
- Susceptibility to cellular stress in PS1 mutant N2a cells is associated with mitochondrial defects and altered calcium homeostasis.Scientific reports · 2020Article
- Alzheimer's Disease Presenilin-1 Mutation Sensitizes Neurons to Impaired Autophagy Flux and Propofol Neurotoxicity: Role of Calcium Dysregulation.Journal of Alzheimer's disease : JAD · 2019Article
- Cilostazol disrupts TLR-4, Akt/GSK-3β/CREB, and IL-6/JAK-2/STAT-3/SOCS-3 crosstalk in a rat model of Huntington's disease.PloS one · 2018Article
- Familial Alzheimer's disease-associated presenilin 1 mutants promote γ-secretase cleavage of STIM1 to impair store-operated Ca2+ entry.Science signaling · 2016Article
- Cellular FLICE-like Inhibitory Protein (c-FLIP) and PS1-associated Protein (PSAP) Mediate Presenilin 1-induced γ-Secretase-dependent and -independent Apoptosis, Respectively.The Journal of biological chemistry · 2015Article
- Mitochondrial succinate dehydrogenase is involved in stimulus-secretion coupling and endogenous ROS formation in murine beta cells.Diabetologia · 2015Article
- Identification of tetrahydrocarbazoles as novel multifactorial drug candidates for treatment of Alzheimer's disease.Translational psychiatry · 2014Article
- Are there roles for brain cell senescence in aging and neurodegenerative disorders?Biogerontology · 2014Review
- Oxidative stress and mitochondrial dysfunction in Alzheimer's disease.Biochimica et biophysica acta · 2014Review
- Neuronal failure in Alzheimer's disease: a view through the oxidative stress looking-glass.Neuroscience bulletin · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Many cases of autosomal dominant early onset Alzheimer's disease (AD) result from mutations in the gene encoding presenilin-1 (PS-1). PS-1 is an integral membrane protein expressed ubiquitously in neurons throughout the brain in which it is located primarily in endoplasmic reticulum (ER). Although the pathogenic mechanism of PS-1 mutations is unknown, recent findings suggest that PS mutations render neurons vulnerable to apoptosis. Because increasing evidence indicates that mitochondrial alterations contribute to neuronal death in AD, we tested the hypothesis that PS-1 mutations sensitize neurons to mitochondrial failure. PC12 cell lines expressing a PS-1 mutation (L286V) exhibited increased sensitivity to apoptosis induced by 3-nitropropionic acid (3-NP) and malonate, inhibitors of succinate dehydrogenase, compared with control cell lines and lines overexpressing wild-type PS-1. The apoptosis-enhancing action of mutant PS-1 was prevented by antioxidants (propyl gallate and glutathione), zVAD-fmk, and cyclosporin A, indicating requirements of reactive oxygen species (ROS), caspases, and mitochondrial permeability transition in the cell death process. 3-NP induced a rapid elevation of [Ca2+]i, which was followed by caspase activation, accumulation of ROS, and decreases in mitochondrial reducing potential and transmembrane potential in cells expressing mutant PS-1. The calcium chelator BAPTA AM and agents that block calcium release from ER and influx through voltage-dependent channels prevented mitochondrial ROS accumulation and membrane depolarization and apoptosis. Our data suggest that by perturbing subcellular calcium homeostasis presenilin mutations sensitize neurons to mitochondria-based forms of apoptosis that involve oxidative stress.
Indexed as
Identifiers
9614221PMC6792705W1611341694What OpenQuestion holds
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.