ArticleThe American journal of pathology2014
Endoplasmic reticulum stress mediates amyloid β neurotoxicity via mitochondrial cholesterol trafficking.
Article in The American journal of pathology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 104 citations in OpenAlex.
- Potential Role of Membrane Contact Sites in the Dysregulation of the Crosstalk Between Mitochondria and Lysosomes in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Membrane lipid composition modulates the organization of VDAC1, a mitochondrial gatekeeper.Communications biology · 2025Article
- Transcriptional Landscape and Biomarker Discovery for Endoplasmic Reticulum Stress in Alzheimer's Disease: An Ex Vivo Study Using Patients-Derived Dermal Fibroblasts.Psychiatry investigation · 2025Article
- New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025Review
- Effects of acute pro-inflammatory stimulation and 25-hydroxycholesterol on hippocampal plasticity and learning involve NLRP3 inflammasome and cellular stress responses.Scientific reports · 2025Article
- Increased Steroidogenic Acute Regulatory Protein Contributes to Cholesterol-induced β-Cell Dysfunction.Endocrinology · 2025Article
- Organelle abnormalities in Alzheimer's disease.Organelle (Tucson, Ariz.) · 2025Article
- Article
- Sertraline modulates hippocampal plasticity via sigma 1 receptors, cellular stress and neurosteroids.Translational psychiatry · 2024Article
- Trajectory of brain-derived amyloid beta in Alzheimer's disease: where is it coming from and where is it going?Translational neurodegeneration · 2024Review
- Endoplasmic reticulum stress signaling modulates ischemia/reperfusion injury in the aged heart by regulating mitochondrial maintenance.Molecular medicine (Cambridge, Mass.) · 2024Review
- Article
- SSRIs differentially modulate the effects of pro-inflammatory stimulation on hippocampal plasticity and memory via sigma 1 receptors and neurosteroids.Translational psychiatry · 2023Article
- Co-administration of Nanowired DL-3-n-Butylphthalide (DL-NBP) Together with Mesenchymal Stem Cells, Monoclonal Antibodies to Alpha Synuclein and TDP-43 (TAR DNA-Binding Protein 43) Enhance Superior Neuroprotection in Parkinson's Disease Following Concussive Head Injury.Advances in neurobiology · 2023Review
- From synapses to circuits and back: Bridging levels of understanding in animal models of Alzheimer's disease.The European journal of neuroscience · 2022Review
- Behavioral and Molecular Effects of Thapsigargin-Induced Brain ER- Stress: Encompassing Inflammation, MAPK, and Insulin Signaling Pathway.Life (Basel, Switzerland) · 2022Article
- Parkin as a Molecular Bridge Linking Alzheimer's and Parkinson's Diseases?Biomolecules · 2022Review
- Nonalcoholic Fatty Liver Disease.Handbook of experimental pharmacology · 2022Review
- A Proinflammatory Stimulus Disrupts Hippocampal Plasticity and Learning via Microglial Activation and 25-Hydroxycholesterol.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Connection Lost, MAM: Errors in ER-Mitochondria Connections in Neurodegenerative Diseases.Brain sciences · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Disrupted cholesterol homeostasis has been reported in Alzheimer disease and is thought to contribute to disease progression by promoting amyloid β (Aβ) accumulation. In particular, mitochondrial cholesterol enrichment has been shown to sensitize to Aβ-induced neurotoxicity. However, the molecular mechanisms responsible for the increased cholesterol levels and its trafficking to mitochondria in Alzheimer disease remain poorly understood. Here, we show that endoplasmic reticulum (ER) stress triggered by Aβ promotes cholesterol synthesis and mitochondrial cholesterol influx, resulting in mitochondrial glutathione (mGSH) depletion in older age amyloid precursor protein/presenilin-1 (APP/PS1) mice. Mitochondrial cholesterol accumulation was associated with increased expression of mitochondrial-associated ER membrane proteins, which favor cholesterol translocation from ER to mitochondria along with specific cholesterol carriers, particularly the steroidogenic acute regulatory protein. In vivo treatment with the ER stress inhibitor 4-phenylbutyric acid prevented mitochondrial cholesterol loading and mGSH depletion, thereby protecting APP/PS1 mice against Aβ-induced neurotoxicity. Similar protection was observed with GSH ethyl ester administration, which replenishes mGSH without affecting the unfolded protein response, thus positioning mGSH depletion downstream of ER stress. Overall, these results indicate that Aβ-mediated ER stress and increased mitochondrial cholesterol trafficking contribute to the pathologic progression observed in old APP/PS1 mice, and that ER stress inhibitors may be explored as therapeutic agents for Alzheimer disease.
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