ArticleAutophagy2021
Upregulation of brain cholesterol levels inhibits mitophagy in Alzheimer disease.
Article in Autophagy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- A dual-targeting mRNA lipid nanoparticle restores ABCA1-dependent cholesterol homeostasis to promote repair of age-related bone defects.Bioactive materials · 2027Article
- Lipid Metabolism in Central Nervous System Diseases: Pathological Mechanisms and Therapeutic Advances.CNS neuroscience & therapeutics · 2026Review
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Molecular mechanisms of exercise-induced improvements in Alzheimer's disease: a focus on lipid homeostasis.Translational neurodegeneration · 2026Review
- SREBF2 enhances lipid metabolism and represses anti-tumor immune responses in cervical cancer by increasing ACAT2.Communications biology · 2026Article
- Carbon-based quantum dots enhance platelets aggregation through migrasomes biogenesis.Journal of nanobiotechnology · 2026Article
- Cells with Defective Mitophagy Do Not Accumulate Atherogenic LDL-Derived Cholesterol.Current medicinal chemistry · 2026Article
- Abnormal cholesterol-cholesteryl ester metabolism impairs mouse oocyte quality during ovarian aging.Cellular & molecular biology letters · 2025Article
- Ginsenoside Rg1 Downregulates miR-9-5p Expression to Modulate SIRT1-Mediated Mitochondrial Dysfunction and Ameliorate Alzheimer's Disease.Molecular neurobiology · 2025Article
- Evolution of Alzheimer's Disease Therapeutics: From Conventional Drugs to Medicinal Plants, Immunotherapy, Microbiotherapy and Nanotherapy.Pharmaceutics · 2025Review
- Insights into targeted ferroptosis in mechanisms, biology, and role of Alzheimer's disease: an update.Frontiers in aging neuroscience · 2025Review
- Article
- Biomarker profiling to determine clinical impact of microRNAs in cognitive disorders.Scientific reports · 2024Article
- Deciphering the effect of phytosterols on Alzheimer's disease and Parkinson's disease: the mediating role of lipid profiles.Alzheimer's research & therapy · 2024Article
- The Multiple Roles of Autophagy in Neural Function and Diseases.Neuroscience bulletin · 2024Review
- Role of lipids in the control of autophagy and primary cilium signaling in neurons.Neural regeneration research · 2024Review
- Cholesterol-dependent amyloid β production: space for multifarious interactions between amyloid precursor protein, secretases, and cholesterol.Cell & bioscience · 2023Review
- Potential role of TREM2 in high cholesterol‑induced cell injury and metabolic dysfunction in SH‑SY5Y cells.Experimental and therapeutic medicine · 2023Article
- Gene Self-Expressive Networks as a Generalization-Aware Tool to Model Gene Regulatory Networks.Biomolecules · 2023Article
- Construction and evaluation of Alzheimer's disease diagnostic prediction model based on genes involved in mitophagy.Frontiers in aging neuroscience · 2023Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial dysfunction is behind several neurodegenerative diseases, including Alzheimer disease (AD). Accumulation of damaged mitochondria is already observed at the early stages of AD and has been linked to impaired mitophagy, but the mechanisms underlying this alteration are still not fully known. In our recent study, we show that intracellular cholesterol enrichment can downregulate amyloid beta (Aβ)-induced mitophagy. Mitochondrial glutathione depletion resulting from high cholesterol levels promotes PINK1 (PTEN induced kinase 1)-mediated mitophagosome formation; however, mitophagy flux is ultimately disrupted, most likely due to fusion deficiency of endosomes-lysosomes caused by cholesterol. Meanwhile, in APP-PSEN1-SREBF2 mice, an AD mouse model that overexpresses the cholesterol-related transcription factor SREBF2, cholesterol accumulation prompts an oxidative- and age-dependent cytosolic aggregation of the mitophagy adaptor OPTN (optineurin), which prevents mitophagosome formation despite enhanced PINK1-PRKN/parkin signaling. Hippocampal neurons from postmortem brain of AD individuals reproduce the progressive accumulation of OPTN in aggresome-like structures accompanied by high levels of mitochondrial cholesterol in advanced stages of the disease. Overall, these data provide new insights into the impairment of the PINK1-PRKN mitophagy pathway in AD and suggest the combination of mitophagy inducers with strategies focused on restoring the cholesterol homeostasis and mitochondrial redox balance as a potential disease-modifying therapy for AD.
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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.