ArticleEMBO molecular medicine2013
Amyloid precursor protein controls cholesterol turnover needed for neuronal activity.
Article in EMBO molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 103 citations in OpenAlex.
- Simvastatin Ameliorates Lipid Metabolism-Mediated Endothelial Inflammation and Tight Junction Impairment in Chronic Cerebral Hypoperfusion.Neuromolecular medicine · 2026Article
- Mitochondria-Associated Membranes: A Key Point of Neurodegenerative Diseases.CNS neuroscience & therapeutics · 2025Review
- Metabolism and metabolomics in senescence, aging, and age-related diseases: a multiscale perspective.Frontiers of medicine · 2025Review
- Early biomarkers in the presymptomatic phase of cognitive impairment: changes in the endocannabinoidome and serotonergic pathways in Alzheimer's-prone mice after mTBI.Acta neuropathologica communications · 2024Article
- Relationships of brain cholesterol and cholesterol biosynthetic enzymes to Alzheimer's pathology and dementia in the CFAS population-derived neuropathology cohort.Neuroscience research · 2024Article
- Cholesterol and Lipid Rafts in the Biogenesis of Amyloid-β Protein and Alzheimer's Disease.Annual review of biophysics · 2024Review
- Towards a Unitary Hypothesis of Alzheimer's Disease Pathogenesis.Journal of Alzheimer's disease : JAD · 2024Article
- Cholesterol-dependent amyloid β production: space for multifarious interactions between amyloid precursor protein, secretases, and cholesterol.Cell & bioscience · 2023Review
- Phospholipase D3 degrades mitochondrial DNA to regulate nucleotide signaling and APP metabolism.Nature communications · 2023Article
- Identifying causal serum protein-cardiometabolic trait relationships using whole genome sequencing.Human molecular genetics · 2023Article
- Lipid metabolism and Alzheimer's disease: clinical evidence, mechanistic link and therapeutic promise.The FEBS journal · 2023Review
- Specific Mutations in the Cholesterol-Binding Site of APP Alter Its Processing and Favor the Production of Shorter, Less Toxic Aβ Peptides.Molecular neurobiology · 2022Article
- Synapse integrity and function: Dependence on protein synthesis and identification of potential failure points.Frontiers in molecular neuroscience · 2022Article
- Cholesterol as a key player in amyloid β-mediated toxicity in Alzheimer's disease.Frontiers in molecular neuroscience · 2022Review
- Regulation of PPARα by APP in Alzheimer disease affects the pharmacological modulation of synaptic activity.JCI insight · 2021Article
- Membrane Cholesterol Is a Critical Determinant for Hippocampal Neuronal Polarity.Frontiers in molecular neuroscience · 2021Article
- Cholesterol and Alzheimer's Disease; From Risk Genes to Pathological Effects.Frontiers in aging neuroscience · 2021Review
- The Alzheimer's disease-associated C99 fragment of APP regulates cellular cholesterol trafficking.The EMBO journal · 2020Article
- SREBP1 silencing inhibits the proliferation and motility of human esophageal squamous carcinoma cells via the Wnt/β-catenin signaling pathway.Oncology letters · 2020Article
- Importance of γ-secretase in the regulation of liver X receptor and cellular lipid metabolism.Life science alliance · 2020Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Perturbation of lipid metabolism favours progression of Alzheimer disease, in which processing of Amyloid Precursor Protein (APP) has important implications. APP cleavage is tightly regulated by cholesterol and APP fragments regulate lipid homeostasis. Here, we investigated whether up or down regulation of full-length APP expression affected neuronal lipid metabolism. Expression of APP decreased HMG-CoA reductase (HMGCR)-mediated cholesterol biosynthesis and SREBP mRNA levels, while its down regulation had opposite effects. APP and SREBP1 co-immunoprecipitated and co-localized in the Golgi. This interaction prevented Site-2 protease-mediated processing of SREBP1, leading to inhibition of transcription of its target genes. A GXXXG motif in APP sequence was critical for regulation of HMGCR expression. In astrocytes, APP and SREBP1 did not interact nor did APP affect cholesterol biosynthesis. Neuronal expression of APP decreased both HMGCR and cholesterol 24-hydroxylase mRNA levels and consequently cholesterol turnover, leading to inhibition of neuronal activity, which was rescued by geranylgeraniol, generated in the mevalonate pathway, in both APP expressing and mevastatin treated neurons. We conclude that APP controls cholesterol turnover needed for neuronal activity.
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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.