ArticleThe EMBO journal2015
Alzheimer's disease-causing proline substitutions lead to presenilin 1 aggregation and malfunction.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Pooled it
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- Isoflurane aggravates pre-existing proteotoxicity in adult nematodes by suppressing mitochondrial fitness.Scientific reports · 2026Article
- Exploring neuroprotective effects of Chuanzhitongluo capsule on an alzheimer's disease rat model.Metabolic brain disease · 2025Article
- Dual modulation of amyloid beta and tau aggregation and dissociation in Alzheimer's disease: a comprehensive review of the characteristics and therapeutic strategies.Translational neurodegeneration · 2025Review
- Inflammatory Bridges: Interconnections Between Alzheimer's Disease and Bone Health.Aging and disease · 2025Review
- Parthanatos drives cognitive decline in repeated brain trauma: MSC-derived exosomes as a novel therapeutic strategy.Frontiers in pharmacology · 2025Article
- A short peptide protects from age-onset proteotoxicity.Aging cell · 2023Article
- Caspase 3 exhibits a yeast metacaspase proteostasis function that protects mitochondria from toxic TDP43 aggregates.Microbial cell (Graz, Austria) · 2023Article
- Article
- Chaperoning activity of the cyclophilin family prevents tau aggregation.Protein science : a publication of the Protein Society · 2022Article
- Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene.International journal of molecular sciences · 2022Review
- Protein degradation-associated mechanisms that are affected in Alzheimer´s disease.Molecular and cellular biochemistry · 2022Review
- [Progress on loss-of-function hypothesis of presenilin-1 mutations in Alzheimer diseases].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2020Article
- Organismal Protein Homeostasis Mechanisms.Genetics · 2020Review
- Alzheimer's Disease, a Lipid Story: Involvement of Peroxisome Proliferator-Activated Receptor α.Cells · 2020Review
- Exploring Alzheimer's Disease Molecular Variability via Calculation of Personalized Transcriptional Signatures.Biomolecules · 2020Article
- MIRRAGGE - Minimum Information Required for Reproducible AGGregation Experiments.Frontiers in molecular neuroscience · 2020Review
- Alzheimer's disease: amyloid-based pathogenesis and potential therapies.Cell stress · 2018Article
- Protein Quality Control in Health and Disease.Cold Spring Harbor perspectives in biology · 2017Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Do different neurodegenerative maladies emanate from the failure of a mutual protein folding mechanism? We have addressed this question by comparing mutational patterns that are linked to the manifestation of distinct neurodegenerative disorders and identified similar neurodegeneration-linked proline substitutions in the prion protein and in presenilin 1 that underlie the development of a prion disorder and of familial Alzheimer's disease (fAD), respectively. These substitutions were found to prevent the endoplasmic reticulum (ER)-resident chaperone, cyclophilin B, from assisting presenilin 1 to fold properly, leading to its aggregation, deposition in the ER, reduction of γ-secretase activity, and impaired mitochondrial distribution and function. Similarly, reduced quantities of the processed, active presenilin 1 were observed in brains of cyclophilin B knockout mice. These discoveries imply that reduced cyclophilin activity contributes to the development of distinct neurodegenerative disorders, propose a novel mechanism for the development of certain fAD cases, and support the emerging theme that this disorder can stem from aberrant presenilin 1 function. This study also points at ER chaperones as targets for the development of counter-neurodegeneration therapies.
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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.