• ADCK3 mutations with epilepsy, stroke-like episodes and ataxia: a POLG mimic? 

      Hikmat, Omar; Tzoulis, Charalampos; Knappskog, Per; Johansson, Stefan; Boman, Helge; Sztromwasser, Pawel Szymon; Lien, Espen; Brodtkorb, Eylert; Ghezzi, Daniele; Bindoff, Laurence (Peer reviewed; Journal article, 2016-07)
      Background and purpose: Defects of coenzyme Q10 (CoQ10) metabolism cause a variety of disorders ranging from isolated myopathy to multisystem involvement. ADCK3 is one of several genes associated with CoQ10 deficiency that ...
    • Base excision repair causes age-dependent accumulation of single-stranded DNA breaks that contribute to Parkinson disease pathology 

      SenGupta, Tanima; Palikaras, Konstantinos; Esbensen, Ying Q.; Konstantinidis, Georgios; Galindo, Francisco Jose Naranjo; Achanta, Kavya; Kassahun, Henok; Stavgiannoudaki, Ioanna; Bohr, Vilhelm A.; Akbari, Mansour; Gaare, Johannes; Tzoulis, Charalampos; Tavernarakis, Nektarios; Nilsen, Hilde (Journal article; Peer reviewed, 2021)
      Aging, genomic stress, and mitochondrial dysfunction are risk factors for neurodegenerative pathologies, such as Parkinson disease (PD). Although genomic instability is associated with aging and mitochondrial impairment, ...
    • Chip protein U-box domain truncation affects Purkinje neuron morphology and leads to behavioral changes in zebrafish 

      Pakdaman, Yasaman; Denker, Elsa; Austad, Eirik; Norton, William H.J.; Rolfsnes, Hans Olav; Bindoff, Laurence Albert; Tzoulis, Charalampos; Aukrust, Ingvild; Knappskog, Per Morten; Johansson, Stefan; Ellingsen, Ståle (Journal article; Peer reviewed, 2021-09-24)
      The ubiquitin ligase CHIP (C-terminus of Hsc70-interacting protein) is encoded by STUB1 and promotes ubiquitination of misfolded and damaged proteins. CHIP deficiency has been linked to several diseases, and mutations in ...
    • Clinical and molecular studies of disease caused by mutations of the mitochondrial DNA polymerase gamma (POLG). 

      Tzoulis, Charalampos (Doctoral thesis, 2010-11-26)
      Background: Mutations in the gene encoding the DNA-polymerase gamma (POLG), the enzyme that replicates and repairs the mitochondrial genome, are an important cause of human disease and disability. Over 130 pathogenic ...
    • Common gene expression signatures in Parkinson’s disease are driven by changes in cell composition 

      Sanchez Nido, Gonzalo; Dick, Fiona; Toker, Lilah; Petersen, Kjell; Alves, Guido Werner; Tysnes, Ole-Bjørn; Jonassen, Inge; Haugarvoll, Kristoffer; Tzoulis, Charalampos (Journal article; Peer reviewed, 2020-04-21)
      The etiology of Parkinson’s disease is largely unknown. Genome-wide transcriptomic studies in bulk brain tissue have identified several molecular signatures associated with the disease. While these studies have the potential ...
    • Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease 

      Dölle, Christian; Flønes, Irene Hana; Sanchez Nido, Gonzalo; Miletic, Hrvoje; Osuagwu, Nelson; Kristoffersen, Stine; Lilleng, Peer Kåre; Larsen, Jan Petter; Tysnes, Ole-Bjørn; Haugarvoll, Kristoffer; Bindoff, Laurence; Tzoulis, Charalampos (Peer reviewed; Journal article, 2016-11-22)
      Increased somatic mitochondrial DNA (mtDNA) mutagenesis causes premature aging in mice, and mtDNA damage accumulates in the human brain with aging and neurodegenerative disorders such as Parkinson disease (PD). Here, we ...
    • Differential transcript usage in the Parkinson’s disease brain 

      Dick, Fiona; Sanchez Nido, Gonzalo; Alves, Guido Werner; Tysnes, Ole-Bjørn; Nilsen, Gry Hilde; Dölle, Christian; Tzoulis, Charalampos (Peer reviewed; Journal article, 2020)
      Studies of differential gene expression have identified several molecular signatures and pathways associated with Parkinson’s disease (PD). The role of isoform switches and differential transcript usage (DTU) remains, ...
    • Disease-specific phenotypes in iPSC-derived neural stem cells with POLG mutations 

      Liang, Xiao; Kristiansen, Cecilie Katrin; Mostafavi, Sepideh; Vatne, Guro H.; Zantingh, Gina; Kianian, Atefeh; Tzoulis, Charalampos; Høyland, Lena Elise; Ziegler, Mathias; Perez, Roberto Megias; Furriol, Jessica; Zhang, Zhuoyuan; Balafkan, Novin; Hong, Yu; Siller, Richard; Sullivan, Gareth; Bindoff, Laurence (Journal article; Peer reviewed, 2020)
      Mutations in POLG disrupt mtDNA replication and cause devastating diseases often with neurological phenotypes. Defining disease mechanisms has been hampered by limited access to human tissues, particularly neurons. Using ...
    • Distinct Mitochondrial Remodeling During Mesoderm Differentiation in a Human-Based Stem Cell Model 

      Mostafavi, Sepideh; Balafkan, Novin; Pettersen, Ina Katrine Nitschke; Nido, Gonzalo Sanchez; Siller, Richard; Tzoulis, Charalampos; Sullivan, Gareth John; Bindoff, Laurence Albert (Journal article; Peer reviewed, 2021-10-14)
      Given the considerable interest in using stem cells for modeling and treating disease, it is essential to understand what regulates self-renewal and differentiation. Remodeling of mitochondria and metabolism, with the shift ...
    • Excellent response of intramedullary Erdheim-Chester disease to vemurafenib: a case report 

      Tzoulis, Charalampos; Schwarzlmüller, Thomas; Søfteland, Eirik; Neckelmann, Gesche; Biermann, Martin; Haroche, Julien; Straume, Oddbjørn; Gjerde, Ivar Otto; Vintermyr, Olav Karsten (Peer reviewed; Journal article, 2015-04-30)
      Background: Erdheim-Chester disease is a rare histiocytosis characterized by multi-systemic organ involvement. Immune-modulating agents such as interferon-alpha have limited success and the disorder is progressive and ...
    • Genome-wide histone acetylation analysis reveals altered transcriptional regulation in the Parkinson’s disease brain 

      Toker, Lilah; Tran, Gia T.; Sundaresan, Janani; Tysnes, Ole-Bjørn; Alves, Guido; Haugarvoll, Kristoffer; Nido, Gonzalo S.; Dölle, Christian; Tzoulis, Charalampos (Journal article; Peer reviewed, 2021)
      Background: Parkinson’s disease (PD) is a complex, age-related neurodegenerative disorder of largely unknown etiology. PD is strongly associated with mitochondrial respiratory dysfunction, which can lead to epigenetic ...
    • In vitro characterization of six STUB1 variants in spinocerebellar ataxia 16 reveals altered structural properties for the encoded CHIP proteins 

      Pakdaman, Yasaman; Sanchez Guixe, Monica; Kleppe, Rune; Erdal, Sigrid; Bustad, Helene J.; Bjørkhaug, Lise; Haugarvoll, Kristoffer; Tzoulis, Charalampos; Heimdal, Ketil Riddervold; Knappskog, Per; Johansson, Stefan; Aukrust, Ingvild (Peer reviewed; Journal article, 2017)
      Spinocerebellar ataxia, autosomal recessive 16 (SCAR16) is caused by biallelic mutations in the STIP1 homology and U-box containing protein 1 (STUB1) gene encoding the ubiquitin E3 ligase and dimeric co-chaperone C-terminus ...
    • LIVE@Home.Path--innovating the clinical pathway for home-dwelling people with dementia and their caregivers: Study protocol for a mixed-method, stepped-wedge, randomized controlled trial 

      Husebø, Bettina; Allore, Heather; Achterberg, Wilco; Angeles, Renira Corinne; Ballard, Clive; Bruvik, Frøydis Kristine; Fæø, Stein Erik; Gedde, Marie H.; Hillestad, Eirin; Jacobsen, Frode F.; Kirkevold, Øyvind; Kjerstad, Egil; Kjome, Reidun Lisbet Skeide; Mannseth, Janne; Naik, Mala; Nouchi, Rui; Puaschitz, Nathalie; Samdal, Rune; Tranvåg, Oscar; Tzoulis, Charalampos; Vahia, Ipsit Vihang; Vislapuu, Maarja; Berge, Line Iden (Journal article; Peer reviewed, 2020)
      Background The global health challenge of dementia is exceptional in size, cost and impact. It is the only top ten cause of death that cannot be prevented, cured or substantially slowed, leaving disease management, caregiver ...
    • Meta-analysis of whole-exome sequencing data from two independent cohorts finds no evidence for rare variant enrichment in Parkinson disease associated loci 

      Gaare, Johannes Jernqvist; Sanchez Nido, Gonzalo; Dölle, Christian; Sztromwasser, Pawel Szymon; Alves, Guido Werner; Tysnes, Ole-Bjørn; Haugarvoll, Kristoffer; Tzoulis, Charalampos (Journal article; Peer reviewed, 2020-10-01)
      Parkinson disease (PD) is a complex neurodegenerative disorder influenced by both environmental and genetic factors. While genome wide association studies have identified several susceptibility loci, many causal variants ...
    • Mitochondrial DNA depletion in sporadic inclusion body myositis 

      Bhatt, Padmanabh S.; Tzoulis, Charalampos; Balafkan, Novin; Miletic, Hrvoje; Tran, Gia Tuong Thi; Sanaker, Petter Schandl; Bindoff, Laurence (Peer reviewed; Journal article, 2019)
      Sporadic inclusion body myositis (sIBM) is a late onset disorder of unkown aetiology. Mitochondrial changes such as cytochrome oxidase deficient fibres are a well recognised feature and mitochondrial DNA (mtDNA) deletions ...
    • Mitochondrial respiratory chain deficiency correlates with the severity of neuropathology in sporadic Creutzfeldt-Jakob disease 

      Flønes, Irene Hana; Ricken, Gerda; Klotz, Sigrid; Lang, Alexandra; Ströbel, Thomas; Dölle, Christian; Kovacs, Gabor G.; Tzoulis, Charalampos (Journal article; Peer reviewed, 2020)
      Mitochondrial dysfunction has been implicated in multiple neurodegenerative diseases but remains largely unexplored in Creutzfeldt-Jakob disease. Here, we characterize the mitochondrial respiratory chain at the individual ...
    • Molecular pathogenesis of polymerase gamma-related neurodegeneration 

      Tzoulis, Charalampos; Tran, Gia Tuong Thi; Coxhead, Jonathan; Bertelsen, Bjørn; Lilleng, Peer Kåre; Balafkan, Novin; Payne, Brendan; Miletic, Hrvoje; Chinnery, Patrick F.; Bindoff, Laurence (Peer reviewed; Journal article, 2014-07)
      Objective: Polymerase gamma (POLG) mutations are a common cause of mitochondrial disease and have also been linked to neurodegeneration and aging. We studied the molecular mechanisms underlying POLG-related neurodegeneration ...
    • MRI characterisation of adult onset alpha-methylacyl-coA racemase deficiency diagnosed by exome sequencing 

      Haugarvoll, Kristoffer; Johansson, Stefan; Tzoulis, Charalampos; Haukanes, Bjørn Ivar; Bredrup, Cecilie; Neckelmann, Gesche; Boman, Helge; Knappskog, Per; Bindoff, Laurence (Peer reviewed; Journal article, 2013-01-03)
      Background: Correct diagnosis is pivotal to understand and treat neurological disease. Herein, we report the diagnostic work-up utilizing exome sequencing and the characterization of clinical features and brain MRI in two ...
    • A multicenter study on Leigh syndrome: disease course and predictors of survival 

      Sofou, Kalliopi; De Coo, Irenaeus F. M.; Isohanni, Pirjo; Ostergaard, Elsebet; Naess, Karin; De Meirleir, Linda; Tzoulis, Charalampos; Uusimaa, Johanna; De Angst, Isabell B.; Lönnqvist, Tuula; Pihko, Helena; Mankinen, Katariina; Bindoff, Laurence; Tulinius, Már; Darin, Niklas (Peer reviewed; Journal article, 2014-04-15)
      Background: Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most ...
    • NSAID use is not associated with Parkinson's disease incidence: A Norwegian Prescription Database study 

      Brakedal, Brage; Tzoulis, Charalampos; Tysnes, Ole-Bjørn; Haugarvoll, Kristoffer (Journal article; Peer reviewed, 2021-09-07)
      Objective: Whether use of nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of incident Parkinson’s disease (PD) remains unresolved. Here, we employed the Norwegian Prescription Database to examine whether NSAID ...