ArticleNeuron2015
Appoptosin-Mediated Caspase Cleavage of Tau Contributes to Progressive Supranuclear Palsy Pathogenesis.
Erratum issuedOpen access · bronzeAbstract read
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Article in Neuron, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 62 papers.
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62citing papers in PubMed
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Who cites it
62 citing papers in PubMed, 101 citations in OpenAlex.
- CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP.Neurology · 2018Trial
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- Biomarkers for Lewy body diseases and other alpha-synucleinopathies in biofluids: current evidence and future directions.Journal of translational medicine · 2025Review
- Rock inhibitors in Alzheimer's disease.Frontiers in aging · 2025Review
- Genetic, transcriptomic, histological, and biochemical analysis of progressive supranuclear palsy implicates glial activation and novel risk genes.Nature communications · 2024Article
- iPSC-induced neurons with the V337M MAPT mutation are selectively vulnerable to caspase-mediated cleavage of tau and apoptotic cell death.Molecular and cellular neurosciences · 2024Article
- Alzheimer's Disease-Related Cerebrospinal Fluid Biomarkers in Progressive Supranuclear Palsy.Brain sciences · 2024Review
- PKCδ serves as a potential biomarker and therapeutic target for microglia-mediated neuroinflammation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Exploring the significance of caspase-cleaved tau in tauopathies and as a complementary pathology to phospho-tau in Alzheimer's disease: implications for biomarker development and therapeutic targeting.Acta neuropathologica communications · 2024Review
- Iron Overload in Brain: Transport Mismatches, Microbleeding Events, and How Nanochelating Therapies May Counteract Their Effects.International journal of molecular sciences · 2024Review
- Prenatal hormone stress triggers embryonic cardiac hypertrophy outcome by ubiquitin-dependent degradation of mitochondrial mitofusin 2.iScience · 2024Article
- ROCK Inhibitor Fasudil Attenuates Neuroinflammation and Associated Metabolic Dysregulation in the Tau Transgenic Mouse Model of Alzheimer's Disease.Current Alzheimer research · 2024Article
- Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease.Frontiers in aging neuroscience · 2024Article
- Glucocorticoid-driven mitochondrial damage stimulates Tau pathology.Brain : a journal of neurology · 2023Article
- Pathological Impact of Tau Proteolytical Process on Neuronal and Mitochondrial Function: a Crucial Role in Alzheimer's Disease.Molecular neurobiology · 2023Review
- Increased level of RAB39B leads to neuronal dysfunction and behavioural changes in mice.Journal of cellular and molecular medicine · 2023Article
- Concomitant Neuronal Tau Deposition and FKBP52 Decrease Is an Early Feature of Different Human and Experimental Tauopathies.Journal of Alzheimer's disease : JAD · 2023Article
- Retromer deficiency in Tauopathy models enhances the truncation and toxicity of Tau.Nature communications · 2022Article
- Caspase-6-cleaved tau is relevant in Alzheimer's disease and marginal in four-repeat tauopathies: Diagnostic and therapeutic implications.Neuropathology and applied neurobiology · 2022Article
- Caspase-cleaved tau is senescence-associated and induces a toxic gain of function by putting a brake on axonal transport.Molecular psychiatry · 2022Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 6 institutions in 4 countries.
Yingjun ZhaoFujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian 361102, China; Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
I-Chu TsengDegenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Charles J HeyserDepartment of Neuroscience, University of California San Diego, La Jolla, CA 92093, USA.
Edward RockensteinDepartment of Neuroscience, University of California San Diego, La Jolla, CA 92093, USA.
Michael ManteDepartment of Neuroscience, University of California San Diego, La Jolla, CA 92093, USA.
Anthony AdameDepartment of Neuroscience, University of California San Diego, La Jolla, CA 92093, USA.
Qiuyang ZhengFujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian 361102, China; Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Timothy HuangDegenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Xin WangFujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
Pharhad E ArslanTanz Centre for Research in Neurodegenerative Diseases, Krembil Discovery Tower, Toronto, ON M5T 2S8, Canada.
Paramita ChakrabartyDepartment of Neuroscience, Center for Translational Research in Neurodegenerative Diseases, University of Florida, Gainesville, FL 32610, USA.
Chengbiao WuDepartment of Neuroscience, University of California San Diego, La Jolla, CA 92093, USA.
Guojun BuFujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian 361102, China.
William C MobleyDepartment of Neuroscience, University of California San Diego, La Jolla, CA 92093, USA.
Yun-Wu ZhangFujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian 361102, China; Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Peter St George-HyslopTanz Centre for Research in Neurodegenerative Diseases, Krembil Discovery Tower, Toronto, ON M5T 2S8, Canada; Department of Medical Biophysics and Medicine (Neurology), University of Toronto, Toronto, ON M5S 3H2, Canada; Department of Clinical Neurosciences, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK.
Eliezer MasliahDepartment of Neuroscience, University of California San Diego, La Jolla, CA 92093, USA; Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA.
Paul FraserTanz Centre for Research in Neurodegenerative Diseases, Krembil Discovery Tower, Toronto, ON M5T 2S8, Canada; Department of Medical Biophysics and Medicine (Neurology), University of Toronto, Toronto, ON M5S 3H2, Canada.
Huaxi XuFujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Xiamen University, Xiamen, Fujian 361102, China; Degenerative Diseases Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. Electronic address: xuh@sbpdiscovery.org.
University of California San Diego · USSanford Burnham Prebys Medical Discovery Institute · USUniversity of Toronto · CAXiamen University · CNDiscovery Centre · CAUniversity of Florida · US
Funding
VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GALASKO, DOUGLAS R · 1985 to 2018
$55.4MTHE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C · 1999 to 2018
$36.9MCenter for Protein Folding Machinery (RMI)PN2EY016525 · NEI · BAYLOR COLLEGE OF MEDICINE · PI CHIU, WAH · 2005 to 2015
$33.6MViral Vectors CoreP01NS074969 · NINDS · WASHINGTON UNIVERSITY · PI HOLTZMAN, DAVID M. · 2012 to 2021
$13.0MRegulation of Protein Trafficking in NeurodegenerationR01NS046673 · NINDS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI XU, HUAXI · 2003 to 2018
$5.8MB-Synuclein as a Treatment for Lewy Body DiseaseR01AG018440 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RISSMAN, ROBERT · 2001 to 2021
$5.2MProject-002P30NS076411 · NINDS · SCINTILLON INSTITUTE FOR PHOTOBIOLOGY · PI LIPTON, STUART A · 2011 to 2016
$4.5MThe Role of Appoptosin in Alzheimer's Disease and Other TauopathiesR01AG038710 · NIA · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI XU, HUAXI · 2011 to 2019
$3.9MApoE Receptor Pathways to Intraneuronal AbetaR01AG027924 · NIA · WASHINGTON UNIVERSITY · PI LI, YONGHE · 2006 to 2021
$3.7MIdentifying genes in Beta-Amyloid ProductionR01AG021173 · NIA · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI XU, HUAXI · 2004 to 2015
$3.3MTRANSGENIC MODELS TO SUDY ALZHEIMERS DISEASER01AG011385 · NIA · SCRIPPS RESEARCH INSTITUTE · PI MUCKE, LENNART · 1992 to 2017
$3.2MGenetic Basis of Failed Cognition in Young and Aged Mouse Models of Trisomy 21R01NS066072 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MOBLEY, WILLIAM C, YU, EUGENE · 2010 to 2014
$3.2MMedical Research Council MC_G1000734NEI NIH HHS PN1 EY016525NEI NIH HHS PN2 EY016525NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG016574NIA NIH HHS R01 AG011385NIA NIH HHS R01 AG018440NIA NIH HHS R01 AG021173NIA NIH HHS R01AG021173NIA NIH HHS R01 AG027924NIA NIH HHS R01 AG035355NIA NIH HHS R01 AG038710NIA NIH HHS R01AG038710NIA NIH HHS R01 AG044420NIA NIH HHS R01AG044420NIA NIH HHS R01AG11385NIA NIH HHS R01AG18440NIA NIH HHS R01AG5131NIA NIH HHS RF1 AG046205NINDS NIH HHS P01 NS074969NINDS NIH HHS P30 NS076411NINDS NIH HHS R01 NS046673NINDS NIH HHS R01NS046673NINDS NIH HHS R01 NS066072NINDS NIH HHS R01NS076411NINDS NIH HHS R01NS66072Wellcome Trust 081864Wellcome Trust 089703
Abstract
Progressive supranuclear palsy (PSP) is a movement disorder characterized by tau neuropathology where the underlying mechanism is unknown. An SNP (rs1768208 C/T) has been identified as a strong risk factor for PSP. Here, we identified a much higher T-allele occurrence and increased levels of the pro-apoptotic protein appoptosin in PSP patients. Elevations in appoptosin correlate with activated caspase-3 and caspase-cleaved tau levels. Appoptosin overexpression increased caspase-mediated tau cleavage, tau aggregation, and synaptic dysfunction, whereas appoptosin deficiency reduced tau cleavage and aggregation. Appoptosin transduction impaired multiple motor functions and exacerbated neuropathology in tau-transgenic mice in a manner dependent on caspase-3 and tau. Increased appoptosin and caspase-3-cleaved tau were also observed in brain samples of patients with Alzheimer's disease and frontotemporal dementia with tau inclusions. Our findings reveal a novel role for appoptosin in neurological disorders with tau neuropathology, linking caspase-3-mediated tau cleavage to synaptic dysfunction and behavioral/motor defects.
Indexed as
AgedAged, 80 and overAge FactorsAlzheimer DiseaseAnimalsApoptosisApoptosis Regulatory ProteinsBrainCaspase 3Cells, CulturedDisease Models, AnimalEmbryo, MammalianFemaleGene Expression RegulationHand StrengthHumansApoptosis Regulatory ProteinsCaspase 3MOBP protein, humanMyelin Proteinstau Proteins
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