ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
The unfolded protein response transcription factor XBP1s ameliorates Alzheimer's disease by improving synaptic function and proteostasis.
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Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 55 citations in OpenAlex.
- XBP1 signaling from tumor metabolic stress to myeloid driven immunotherapy resistance (Review).International journal of molecular medicine · 2026Review
- Long-Term Impact of Historical BCG Vaccination Policies on Parkinson's Disease Risk: A Hypothesis-Generating Retrospective Cohort Analysis.Biomedicines · 2026Article
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Adaptive inter-tissue proteostasis networks in aging and neurodegeneration.Bioscience reports · 2026Review
- Microglial state transitions are constrained by developmental and metabolic checkpoints.Frontiers in cellular neuroscience · 2026Review
- Adaptive-to-maladaptive IRE1α signaling as a driver of amyloidogenic APP processing in Alzheimer's disease.Frontiers in molecular biosciences · 2026Review
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- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- A novel prognostic model based on endoplasmic reticulum stress-associated E3 ligases and deubiquitinating enzymes in hepatocellular carcinoma.Translational cancer research · 2025Article
- Bezafibrate treatment rescues neurodevelopmental and neurodegenerative defects in 3D cortical organoid model of MAPT frontotemporal dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Diabetic retinopathy and Alzheimer's disease: Convergence of the unfolded protein response in neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Activation of XBP1s attenuates disease severity in models of proteotoxic Charcot-Marie-Tooth type 1B.Brain : a journal of neurology · 2025Article
- Tyrosinase-induced neuromelanin accumulation triggers rapid dysregulation and degeneration of the mouse locus coeruleus.bioRxiv : the preprint server for biology · 2025Article
- Artificial enforcement of the unfolded protein response reduces disease features in multiple preclinical models of ALS/FTD.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- Significance of gene therapy in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- Endoplasmic Reticulum Stress in Neurodegenerative Diseases.Journal of dementia and alzheimer's disease · 2024Article
- Protein Glycosylation Patterns Shaped By the IRE1-XBP1s Arm of the Unfolded Protein Response.Israel journal of chemistry · 2024Article
- RTP801 interacts with the tRNA ligase complex and dysregulates its RNA ligase activity in Alzheimer's disease.Nucleic acids research · 2024Article
- Essential roles of the unfolded protein response in intestinal physiology.eGastroenterology · 2024Review
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Authors and funding
29 authors at 8 institutions in 4 countries.
Claudia Duran-AniotzBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Latin American Institute for Brain Health (BrainLat), Universidad Adolfo Ibáñez, Santiago, Chile; Center for Social and Cognitive Neuroscience (CSCN), School of Psychology, Universidad Adolfo Ibanez, Santiago, Chile. Electronic address: claudia.duran@uai.cl.
Natalia PobleteBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Catalina Rivera-KrstulovicBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Álvaro O ArdilesCentro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile.
Mei Li Díaz-HungBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Giovanni TamburiniBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Carleen Mae P SabusapDepartment of Chemistry and Biological Sciences, Vanderbilt University, Nashville, TN, USA.
Yannis GerakisBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Felipe Cabral-MirandaBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Javier DiazBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Matias FuentealbaBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Diego ArriagadaBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Ernesto MuñozFONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Department of Biology, Faculty of Sciences and Department of Neurosciences, Faculty of Medicina, Universidad de Chile, Santiago, Chile.
Sandra EspinozaBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Gabriela MartinezBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Gabriel QuirozBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Pablo SardiRare and Neurological Diseases Therapeutic Area, Sanofi, Framingham, MA, USA.
Danilo B MedinasBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Darwin ContrerasLaboratory of Neuroscience, Department of Biology, Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile.
Ricardo PiñaLaboratory of Neuroscience, Department of Biology, Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile.
Mychael V LourencoInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Felipe C RibeiroInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Sergio T FerreiraInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; D'Or Institute for Research and Education, Rio de Janeiro, Brazil.
Carlos RozasLaboratory of Neuroscience, Department of Biology, Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile.
Bernardo MoralesLaboratory of Neuroscience, Department of Biology, Faculty of Chemistry and Biology, University of Santiago de Chile, Santiago, Chile.
Lars PlateDepartment of Chemistry and Biological Sciences, Vanderbilt University, Nashville, TN, USA.
Christian Gonzalez-BillaultFONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Department of Biology, Faculty of Sciences and Department of Neurosciences, Faculty of Medicina, Universidad de Chile, Santiago, Chile.
Adrian G PalaciosCentro Interdisciplinario de Neurociencia de Valparaíso, Universidad de Valparaíso, Valparaíso, Chile.
Claudio HetzBiomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago, Chile; FONDAP Center for Geroscience, Brain Health, and Metabolism (GERO), Santiago, Chile; Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile; Buck Institute for Research on Aging, Novato, CA 94945, USA. Electronic address: chetz@uchile.cl.
Center for Climate and Resilience Research · CLUniversidad de Santiago de Chile · CLUniversidade Federal do Rio de Janeiro · BRUniversity of Valparaíso · CLVanderbilt University · USAdolfo Ibáñez University · CLBuck Institute for Research on Aging · USSanofi (United States) · US
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alteration in the buffering capacity of the proteostasis network is an emerging feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is the main adaptive pathway to cope with protein folding stress at the ER. Inositol-requiring enzyme-1 (IRE1) operates as a central ER stress sensor, enabling the establishment of adaptive and repair programs through the control of the expression of the transcription factor X-box binding protein 1 (XBP1). To artificially enforce the adaptive capacity of the UPR in the AD brain, we developed strategies to express the active form of XBP1 in the brain. Overexpression of XBP1 in the nervous system using transgenic mice reduced the load of amyloid deposits and preserved synaptic and cognitive function. Moreover, local delivery of XBP1 into the hippocampus of an 5xFAD mice using adeno-associated vectors improved different AD features. XBP1 expression corrected a large proportion of the proteomic alterations observed in the AD model, restoring the levels of several synaptic proteins and factors involved in actin cytoskeleton regulation and axonal growth. Our results illustrate the therapeutic potential of targeting UPR-dependent gene expression programs as a strategy to ameliorate AD features and sustain synaptic function.
Indexed as
Alzheimer DiseaseAnimalsEndoplasmic Reticulum StressMiceMice, TransgenicProteomicsProteostasisSignal TransductionTranscription FactorsUnfolded Protein ResponseX-Box Binding Protein 1Transcription FactorsX-Box Binding Protein 1Xbp1 protein, mouseAlzheimer’s diseaseamyloid βER stressUPRXBP1
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