ArticleAging cell2014
Upregulation of PGC-1α expression by Alzheimer's disease-associated pathway: presenilin 1/amyloid precursor protein (APP)/intracellular domain of APP.
Article in Aging cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.Aging and disease · 2024Review
- Study insights in the role of PGC-1α in neurological diseases: mechanisms and therapeutic potential.Frontiers in aging neuroscience · 2024Review
- Mitochondria in health, disease, and aging.Physiological reviews · 2023Review
- Interdisciplinary Approaches to Deal with Alzheimer's Disease-From Bench to Bedside: What Feasible Options Do Already Exist Today?Biomedicines · 2022Review
- Recent Advances in Molecular Pathways and Therapeutic Implications Targeting Mitochondrial Dysfunction for Alzheimer's Disease.Molecular neurobiology · 2022Review
- Targeted Lipidomics of Mitochondria in a Cellular Alzheimer's Disease Model.Biomedicines · 2021Article
- Shotgun lipidomics of liver and brain tissue of Alzheimer's disease model mice treated with acitretin.Scientific reports · 2021Article
- Reappraisal of metabolic dysfunction in neurodegeneration: Focus on mitochondrial function and calcium signaling.Acta neuropathologica communications · 2021Review
- Melanocortin 1 receptor attenuates early brain injury following subarachnoid hemorrhage by controlling mitochondrial metabolismTheranostics · 2021Article
- Regulatory feedback cycle of the insulin-degrading enzyme and the amyloid precursor protein intracellular domain: Implications for Alzheimer's disease.Aging cell · 2020Article
- Mitochondria dysfunction in the pathogenesis of Alzheimer's disease: recent advances.Molecular neurodegeneration · 2020Review
- A Role for PGC-1α in Transcription and Excitability of Neocortical and Hippocampal Excitatory Neurons.Neuroscience · 2020Article
- Article
- A key role for MAM in mediating mitochondrial dysfunction in Alzheimer disease.Cell death & disease · 2018Review
- MH84 improves mitochondrial dysfunction in a mouse model of early Alzheimer's disease.Alzheimer's research & therapy · 2018Article
- A Novel Tetramethylpyrazine Derivative Protects Against Glutamate-Induced Cytotoxicity Through PGC1α/Nrf2 and PI3K/Akt Signaling Pathways.Frontiers in neuroscience · 2018Article
- Omega-3 fatty acids, lipids, and apoE lipidation in Alzheimer's disease: a rationale for multi-nutrient dementia prevention.Journal of lipid research · 2017Review
- Expression of TAG1/APP signaling pathway in the proliferation and differentiation of glioma stem cells.Oncology letters · 2017Article
- Mitochondrial Proteome Changes Correlating with β-Amyloid Accumulation.Molecular neurobiology · 2017Article
- Phytosterols and Dementia.Plant foods for human nutrition (Dordrecht, Netherlands) · 2016Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cleavage of amyloid precursor protein (APP) by β- and γ-secretase generates amyloid-β (Aβ) and APP intracellular domain (AICD) peptides. Presenilin (PS) 1 or 2 is the catalytic component of the γ-secretase complex. Mitochondrial dysfunction is an established phenomenon in Alzheimer's disease (AD), but the causes and role of PS1, APP, and APP's cleavage products in this process are largely unknown. We studied the effect of these AD-associated molecules on mitochondrial features. Using cells deficient in PSs expression, expressing human wild-type PS1, or PS1 familial AD (FAD) mutants, we found that PS1 affects mitochondrial energy metabolism (ATP levels and oxygen consumption) and expression of mitochondrial proteins. These effects were associated with enhanced expression of the mitochondrial master transcriptional coactivator PGC-1α and its target genes. Importantly, PS1-FAD mutations decreased PS1's ability to enhance PGC-1α mRNA levels. Analyzing the effect of APP and its γ-secretase-derived cleavage products Aβ and AICD on PGC-1α expression showed that APP and AICD increase PGC-1α expression. Accordingly, PGC-1α mRNA levels in cells deficient in APP/APLP2 or expressing APP lacking its last 15 amino acids were lower than in control cells, and treatment with AICD, but not with Aβ, enhanced PGC-1α mRNA levels in these and PSs-deficient cells. In addition, knockdown of the AICD-binding partner Fe65 reduced PGC-1α mRNA levels. Importantly, APP/AICD increases PGC-1α expression also in the mice brain. Our results therefore suggest that APP processing regulates mitochondrial function and that impairments in the newly discovered PS1/APP/AICD/PGC-1α pathway may lead to mitochondrial dysfunction and neurodegeneration.
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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.