ArticleCell death discovery2022
Accumulation of APP-CTF induces mitophagy dysfunction in the iNSCs model of Alzheimer's disease.
Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- Presynaptic accumulation of APP-CTFβ may contribute to synaptic dysfunction in Alzheimer's disease.The EMBO journal · 2026Article
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- Functional relationships linking C99/APP-βCTF dimerization, proteostasis disruption, and organelle dysfunction.Cell communication and signaling : CCS · 2026Article
- Therapeutic Options for Alzheimer's Disease and Aging-Associated Cognitive Decline: State of the Art in the ACH2.0 Paradigm.International journal of molecular sciences · 2026Review
- Investigating the molecular mechanisms of glutamine metabolism and mitochondria-related biomarkers in Alzheimer's disease through transcriptomics and experimental validation.European journal of medical research · 2026Article
- Alzheimer's Disease-Associated Amyloid-β Precursor Protein Prevents Aging Stress-Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity.Cancer research · 2025Article
- Alzheimer's Is a Multiform Disease of Sustained Neuronal Integrated Stress Response Driven by the C99 Fragment Generated Independently of AβPP; Proteolytic Production of Aβ Is Suppressed in AD-Affected Neurons: Evolution of a Theory.International journal of molecular sciences · 2025Review
- Article
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- Mitochondrial quality control disorder in neurodegenerative disorders: Potential and advantages of traditional Chinese medicines.Journal of pharmaceutical analysis · 2025Review
- How the gut microbiota impacts neurodegenerative diseases by modulating CNS immune cells.Journal of neuroinflammation · 2025Review
- Investigating Connectivity Deficits in Alzheimer's Disease Using a Novel 3D Bioprinted Model Designed to Quantify Neurite Outgrowth.Bioengineering (Basel, Switzerland) · 2025Article
- N-tert-Butylhydroxylamine promotes melanin production in oxidative stress conditions through the MITF signaling pathway.Archives of dermatological research · 2025Article
- Article
- Article
- MAMs and Mitochondrial Quality Control: Overview and Their Role in Alzheimer's Disease.Neurochemical research · 2024Review
- Mitochondrial alterations in fibroblasts from sporadic Alzheimer's disease (AD) patients correlate with AD-related clinical hallmarks.Acta neuropathologica communications · 2024Article
- The amyloid precursor protein and its derived fragments concomitantly contribute to the alterations of mitochondrial transport machinery in Alzheimer's disease.Cell death & disease · 2024Article
- Promoting Alzheimer's disease research and therapy with stem cell technology.Stem cell research & therapy · 2024Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
Abstract
Mitochondrial dysfunction is associated with familial Alzheimer's disease (fAD), and the accumulation of damaged mitochondria has been reported as an initial symptom that further contributes to disease progression. In the amyloidogenic pathway, the amyloid precursor protein (APP) is cleaved by β-secretase to generate a C-terminal fragment, which is then cleaved by γ-secretase to produce amyloid-beta (Aβ). The accumulation of Aβ and its detrimental effect on mitochondrial function are well known, yet the amyloid precursor protein-derived C-terminal fragments (APP-CTFs) contributing to this pathology have rarely been reported. We demonstrated the effects of APP-CTFs-related pathology using induced neural stem cells (iNSCs) from AD patient-derived fibroblasts. APP-CTFs accumulation was demonstrated to mainly occur within mitochondrial domains and to be both a cause and a consequence of mitochondrial dysfunction. APP-CTFs accumulation also resulted in mitophagy failure, as validated by increased LC3-II and p62 and inconsistent PTEN-induced kinase 1 (PINK1)/E3 ubiquitin ligase (Parkin) recruitment to mitochondria and failed fusion of mitochondria and lysosomes. The accumulation of APP-CTFs and the causality of impaired mitophagy function were also verified in AD patient-iNSCs. Furthermore, we confirmed this pathological loop in presenilin knockout iNSCs (PSEN KO-iNSCs) because APP-CTFs accumulation is due to γ-secretase blockage and similarly occurs in presenilin-deficient cells. In the present work, we report that the contribution of APP-CTFs accumulation is associated with mitochondrial dysfunction and mitophagy failure in AD patient-iNSCs as well as PSEN KO-iNSCs.
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What 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.