دورية أكاديمية

PSMF1 variants cause a phenotypic spectrum from early-onset Parkinson's disease to perinatal lethality by disrupting mitochondrial pathways.

التفاصيل البيبلوغرافية
العنوان: PSMF1 variants cause a phenotypic spectrum from early-onset Parkinson's disease to perinatal lethality by disrupting mitochondrial pathways.
المؤلفون: Magrinelli F; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom., Tesson C; Institut du Cerveau et de la Moelle épinière, ICM, Inserm, CNRS, Sorbonne Université, Paris, France., Angelova PR; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom., Salazar-Villacorta A; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom., Rodriguez JA; Laboratory of Apoptosis and Cancer Biology, The Rockefeller University, New York, NY, USA., Scardamaglia A; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom., Chung BH; Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.; Hong Kong Genome Institute, Hong Kong SAR, China., Jaconelli M; Medical Research Council (MRC) Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Vona B; Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.; Institute for Auditory Neuroscience and Inner Ear Lab, University Medical Center Göttingen, Göttingen, Germany., Esteras N; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.; Neurochemistry Research Institute, Department of Biochemistry and Molecular Biology, School of Medicine, Complutense University of Madrid, Madrid, Spain.; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, Madrid, Spain., Kwong AK; Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Courtin T; Institut du Cerveau et de la Moelle épinière, ICM, Inserm, CNRS, Sorbonne Université, Paris, France., Maroofian R; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom., Alavi S; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom., Nirujogi R; Medical Research Council (MRC) Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Severino M; Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genova, Italy., Lewis PA; Royal Veterinary College, London, United Kingdom.; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom., Efthymiou S; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom., O'Callaghan B; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom., Buchert R; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany., Sofan L; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany., Lis P; Medical Research Council (MRC) Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Pinon C; Institut du Cerveau et de la Moelle épinière, ICM, Inserm, CNRS, Sorbonne Université, Paris, France., Breedveld GJ; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands., Chui MM; Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Murphy D; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom., Pitz V; Integrative Neurogenomics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA., Makarious MB; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA., Cassar M; Institut du Cerveau et de la Moelle épinière, ICM, Inserm, CNRS, Sorbonne Université, Paris, France., Hassan BA; Institut du Cerveau et de la Moelle épinière, ICM, Inserm, CNRS, Sorbonne Université, Paris, France., Iftikhar S; Department of Real-World evidence studies, CENTOGENE GmbH, Rostock, Germany., Rocca C; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom., Bauer P; Department of Medical Genetics, CENTOGENE GmbH, Rostock, Germany., Tinazzi M; Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy., Svetel M; Movement Disorders Department, Neurology Clinic, University Clinical Center of Serbia, Belgrade, Serbia., Samanci B; Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Hanağası HA; Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Bilgiç B; Behavioral Neurology and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey., Obeso JA; CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, Madrid, Spain.; HM CINAC, Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, Spain.; University CEU-San Pablo, Madrid, Spain., Kurtis MM; Neurology Department, Hospital Ruber Internacional, Madrid, Spain., Cogan G; Institut du Cerveau et de la Moelle épinière, ICM, Inserm, CNRS, Sorbonne Université, Paris, France., Başak AN; Koç University, School of Medicine, Research Center for Translational Medicine KUTTAM-Neurodegeneration Research Laboratory NDAL, Istanbul, Turkey., Kiziltan G; Department of Neurology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey., Gül T; Koç University, School of Medicine, Research Center for Translational Medicine KUTTAM-Neurodegeneration Research Laboratory NDAL, Istanbul, Turkey., Yalçın G; Department of Neurology, School of Medicine, Hacettepe University, Ankara, Turkey., Elibol B; Department of Neurology, School of Medicine, Hacettepe University, Ankara, Turkey., Barišić N; Department of Pediatrics, University of Zagreb Medical School and University Hospital Center Zagreb, Zagreb, Croatia., Ng EW; Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Fan SS; Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Hershkovitz T; The Genetics Institute, Galilee Medical Center, Nahariya, Israel., Weiss K; Genetics Institute, Rambam Health Care Center, Haifa, Israel.; Ruth and Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel., Raza Alvi J; Department of Paediatric Neurology, The Children's Hospital and the University of Child Health Sciences, Lahore, Punjab, Pakistan., Sultan T; Department of Paediatric Neurology, The Children's Hospital and the University of Child Health Sciences, Lahore, Punjab, Pakistan., Azmi Alkhawaja I; Pediatric Neurology Unit, Pediatric Department, Albashir Hospital, Amman, Jordan., Froukh T; Department of Biotechnology and Genetics Engineering, Philadelphia University, Jordan., E Alrukban HA; Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia., Fauth C; Institute of Human Genetics, Medical University Innsbruck, Innsbruck, Austria., Schatz UA; Institute of Human Genetics, Medical University Innsbruck, Innsbruck, Austria.; Institute of Human Genetics, School of Medicine and Health, Technical University of Munich, Munich, Germany., Zöggeler T; Department of Pediatrics I, Medical University Innsbruck, Innsbruck, Austria., Zech M; Institute of Human Genetics, School of Medicine and Health, Technical University of Munich, Munich, Germany.; Institute of Neurogenomics, Helmholtz Zentrum Munich, Munich, Germany.; Institute for Advanced Study, Technical University of Munich, Garching, Germany., Stals K; Exeter Genomics Laboratory, Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom., Varghese V; All Wales Medical Genomics Service, Cardiff, United Kingdom., Gandhi S; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.; The Francis Crick Institute, London, United Kingdom., Blauwendraat C; Integrative Neurogenomics Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA., Hardy JA; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom., Lesage S; Institut du Cerveau et de la Moelle épinière, ICM, Inserm, CNRS, Sorbonne Université, Paris, France., Bonifati V; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands., Haack TB; Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany.; Institute of Neurogenomics, Helmholtz Zentrum Munich, Munich, Germany., Bertoli-Avella AM; Department of Medical Genetics, CENTOGENE GmbH, Rostock, Germany., Steinfeld R; Department of Pediatrics and Pediatric Neurology, University of Göttingen, Göttingen, Germany.; Department of Pediatric Neurology, Charité University Medicine, Berlin, Germany., Alessi DR; Medical Research Council (MRC) Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom., Steller H; Laboratory of Apoptosis and Cancer Biology, The Rockefeller University, New York, NY, USA., Brice A; Institut du Cerveau et de la Moelle épinière, ICM, Inserm, CNRS, Sorbonne Université, Paris, France., Abramov AY; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom., Bhatia KP; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom., Houlden H; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom.
المصدر: MedRxiv : the preprint server for health sciences [medRxiv] 2024 Jun 20. Date of Electronic Publication: 2024 Jun 20.
نوع المنشور: Journal Article; Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101767986 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: medRxiv Subsets: PubMed not MEDLINE
مستخلص: Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify PSMF1 as a new gene implicated in PD and childhood neurodegeneration. We find that biallelic PSMF1 missense and loss-of-function variants co-segregate with phenotypes from early-onset PD and parkinsonism to perinatal lethality with neurological manifestations across 15 unrelated pedigrees with 22 affected subjects, showing clear genotype-phenotype correlation. PSMF1 encodes the proteasome regulator PSMF1/PI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate that PSMF1 variants impair mitochondrial membrane potential, dynamics and mitophagy in patient-derived fibroblasts. Additionally, we develop models of psmf1 knockdown Drosophila and Psmf1 conditional knockout mouse exhibiting age-dependent motor impairment, with diffuse gliosis in mice. These findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest mitochondrial dysfunction as a mechanistic contributor.
تواريخ الأحداث: Date Created: 20240816 Latest Revision: 20240826
رمز التحديث: 20240826
مُعرف محوري في PubMed: PMC11326324
DOI: 10.1101/2024.06.19.24308302
PMID: 39148840
قاعدة البيانات: MEDLINE
الوصف
DOI:10.1101/2024.06.19.24308302