ArticlePloS one2013
Turnover of C99 is controlled by a crosstalk between ERAD and ubiquitin-independent lysosomal degradation in human neuroglioma cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Functional relationships linking C99/APP-βCTF dimerization, proteostasis disruption, and organelle dysfunction.Cell communication and signaling : CCS · 2026Article
- APP-C31 pathology as a target in neurodegenerative diseases.Journal of biomedical science · 2026Review
- Enhanced cleavage of APP by co-expressed Bace1 alters the distribution of APP and its fragments in neuronal and non-neuronal cells.Molecular neurobiology · 2022Article
- Review
- Roles of Selenoproteins in Brain Function and the Potential Mechanism of Selenium in Alzheimer's Disease.Frontiers in neuroscience · 2021Review
- GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation.International journal of molecular sciences · 2020Article
- Exploring the Promise of Targeting Ubiquitin-Proteasome System to Combat Alzheimer's Disease.Neurotoxicity research · 2020Review
- Article
- Attempt to Untangle the Prion-Like Misfolding Mechanism for Neurodegenerative Diseases.International journal of molecular sciences · 2018Review
- Interplay Between the Autophagy-Lysosomal Pathway and the Ubiquitin-Proteasome System: A Target for Therapeutic Development in Alzheimer's Disease.Frontiers in cellular neuroscience · 2018Review
- Herpes Simplex Virus Type 1 Enhances Expression of the Synaptic Protein Arc for Its Own Benefit.Frontiers in cellular neuroscience · 2018Article
- Disruption of amyloid precursor protein ubiquitination selectively increases amyloid β (Aβ) 40 levels via presenilin 2-mediated cleavage.The Journal of biological chemistry · 2017Article
- Amyloid precursor protein and endosomal-lysosomal dysfunction in Alzheimer's disease: inseparable partners in a multifactorial disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Review
- Cyclic cis-Locked Phospho-Dipeptides Reduce Entry of AβPP into Amyloidogenic Processing Pathway.Journal of Alzheimer's disease : JAD · 2017Article
- The Endosome-associated Deubiquitinating Enzyme USP8 Regulates BACE1 Enzyme Ubiquitination and Degradation.The Journal of biological chemistry · 2016Article
- Tetrahydrohyperforin (IDN5706) targets the endoplasmic reticulum for autophagy activation: potential mechanism for Alzheimer's disease therapy.Neural regeneration research · 2016Article
- The adipocyte differentiation protein APMAP is an endogenous suppressor of Aβ production in the brain.Human molecular genetics · 2015Article
- Article
- Identification and Preclinical Pharmacology of the γ-Secretase Modulator BMS-869780.International journal of Alzheimer's disease · 2014Article
- Triptolide preserves cognitive function and reduces neuropathology in a mouse model of Alzheimer's disease.PloS one · 2014Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is characterized by the buildup of amyloid-β peptides (Aβ) aggregates derived from proteolytic processing of the β-amyloid precursor protein (APP). Amyloidogenic cleavage of APP by β-secretase/BACE1 generates the C-terminal fragment C99/CTFβ that can be subsequently cleaved by γ-secretase to produce Aβ. Growing evidence indicates that high levels of C99/CTFβ are determinant for AD. Although it has been postulated that γ-secretase-independent pathways must control C99/CTFβ levels, the contribution of organelles with degradative functions, such as the endoplasmic reticulum (ER) or lysosomes, is unclear. In this report, we investigated the turnover and amyloidogenic processing of C99/CTFβ in human H4 neuroglioma cells, and found that C99/CTFβ is localized at the Golgi apparatus in contrast to APP, which is mostly found in endosomes. Conditions that localized C99/CTFβ to the ER resulted in its degradation in a proteasome-dependent manner that first required polyubiquitination, consistent with an active role of the ER associated degradation (ERAD) in this process. Furthermore, when proteasomal activity was inhibited C99/CTFβ was degraded in a chloroquine (CQ)-sensitive compartment, implicating lysosomes as alternative sites for its degradation. Our results highlight a crosstalk between degradation pathways within the ER and lysosomes to avoid protein accumulation and toxicity.
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