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    7986 results match your criteria Acta neuropathologica[Journal]

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    The neuroprotective transcription factor ATF5 is decreased and sequestered into polyglutamine inclusions in Huntington's disease.
    Acta Neuropathol 2017 Aug 31. Epub 2017 Aug 31.
    Centro de Biología Molecular Severo Ochoa (CBMSO) CSIC/UAM, Madrid, Spain.
    Activating transcription factor-5 (ATF5) is a stress-response transcription factor induced upon different cell stressors like fasting, amino-acid limitation, cadmium or arsenite. ATF5 is also induced, and promotes transcription of anti-apoptotic target genes like MCL1, during the unfolded protein response (UPR) triggered by endoplasmic reticulum stress. In the brain, high ATF5 levels are found in gliomas and also in neural progenitor cells, which need to decrease their ATF5 levels for differentiation into mature neurons or glia. Read More

    Distinct molecular profile of diffuse cerebellar gliomas.
    Acta Neuropathol 2017 Aug 29. Epub 2017 Aug 29.
    Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
    Recent studies have demonstrated that tumor-driving alterations are often different among gliomas that originated from different brain regions and have underscored the importance of analyzing molecular characteristics of gliomas stratified by brain region. Therefore, to elucidate molecular characteristics of diffuse cerebellar gliomas (DCGs), 27 adult, mostly glioblastoma cases were analyzed. Comprehensive analysis using whole-exome sequencing, RNA sequencing, and Infinium methylation array (n = 17) demonstrated their distinct molecular profile compared to gliomas in other brain regions. Read More

    MSA prions exhibit remarkable stability and resistance to inactivation.
    Acta Neuropathol 2017 Aug 28. Epub 2017 Aug 28.
    Institute for Neurodegenerative Diseases, Weill Institute for Neurosciences, University of California, 675 Nelson Rising Lane, San Francisco, CA, 94158, USA.
    In multiple system atrophy (MSA), progressive neurodegeneration results from the protein α-synuclein misfolding into a self-templating prion conformation that spreads throughout the brain. MSA prions are transmissible to transgenic (Tg) mice expressing mutated human α-synuclein (TgM83(+/-)), inducing neurological disease following intracranial inoculation with brain homogenate from deceased patient samples. Noting the similarities between α-synuclein prions and PrP scrapie (PrP(Sc)) prions responsible for Creutzfeldt-Jakob disease (CJD), we investigated MSA transmission under conditions known to result in PrP(Sc) transmission. Read More

    The 2017 World Health Organization classification of tumors of the pituitary gland: a summary.
    Acta Neuropathol 2017 Aug 18. Epub 2017 Aug 18.
    Departments of Pathology and Neurological Surgery, University of Virginia School of Medicine, 1215 Lee Street-Room 3060-HEP, Charlottesville, VA, 22908-0214, USA.
    The 4th edition of the World Health Organization (WHO) classification of endocrine tumors has been recently released. In this new edition, major changes are recommended in several areas of the classification of tumors of the anterior pituitary gland (adenophypophysis). The scope of the present manuscript is to summarize these recommended changes, emphasizing a few significant topics. Read More

    Conserved DNA methylation combined with differential frontal cortex and cerebellar expression distinguishes C9orf72-associated and sporadic ALS, and implicates SERPINA1 in disease.
    Acta Neuropathol 2017 Aug 14. Epub 2017 Aug 14.
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
    We previously found C9orf72-associated (c9ALS) and sporadic amyotrophic lateral sclerosis (sALS) brain transcriptomes comprise thousands of defects, among which, some are likely key contributors to ALS pathogenesis. We have now generated complementary methylome data and combine these two data sets to perform a comprehensive "multi-omic" analysis to clarify the molecular mechanisms initiating RNA misregulation in ALS. We found that c9ALS and sALS patients have generally distinct but overlapping methylome profiles, and that the c9ALS- and sALS-affected genes and pathways have similar biological functions, indicating conserved pathobiology in disease. Read More

    Alpha-synuclein oligomers: a new hope.
    Acta Neuropathol 2017 Aug 12. Epub 2017 Aug 12.
    Department of Physiology, Anatomy and Genetics, Oxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford, OX1 3QT, UK.
    Alpha-synuclein is a protein implicated in Parkinson's disease and thought to be one of the main pathological drivers in the disease, although it remains unclear how this protein elicits its neurotoxic effects. Recent findings indicate that the assembly of toxic oligomeric species of alpha-synuclein may be one of the key processes for the pathology and spread of the disease. The absence of a sensitive in situ detection method has hindered the study of these oligomeric species and the role they play in the human brain until recently. Read More

    A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8.
    Acta Neuropathol 2017 Aug 5. Epub 2017 Aug 5.
    Peripheral Neuropathy Research Group, Department of Biomedical Sciences and Institute Born Bunge, University of Antwerp, Universiteitsplein 1, 2610, Antwerpen, Belgium.
    Mutations in the small heat shock protein B8 gene (HSPB8/HSP22) have been associated with distal hereditary motor neuropathy, Charcot-Marie-Tooth disease, and recently distal myopathy. It is so far not clear how mutant HSPB8 induces the neuronal and muscular phenotypes and if a common pathogenesis lies behind these diseases. Growing evidence points towards a role of HSPB8 in chaperone-associated autophagy, which has been shown to be a determinant for the clearance of poly-glutamine aggregates in neurodegenerative diseases but also for the maintenance of skeletal muscle myofibrils. Read More

    Angiocentric glioma with MYB-QKI fusion located in the brainstem, rather than cerebral cortex.
    Acta Neuropathol 2017 Aug 3. Epub 2017 Aug 3.
    Department of Pathology, University of California, San Francisco, 513 Parnassus Ave, Health Sciences West 451, San Francisco, CA, 94143, USA.

    RNAi screen identifies essential regulators of human brain metastasis-initiating cells.
    Acta Neuropathol 2017 Aug 1. Epub 2017 Aug 1.
    MDCL 5027, Stem Cell and Cancer Research Institute, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada.
    Brain metastases (BM) are the most common brain tumor in adults and are a leading cause of cancer mortality. Metastatic lesions contain subclones derived from their primary lesion, yet their functional characterization is limited by a paucity of preclinical models accurately recapitulating the metastatic cascade, emphasizing the need for a novel approach to BM and their treatment. We identified a unique subset of stem-like cells from primary human patient brain metastases, termed brain metastasis-initiating cells (BMICs). Read More

    The choroid plexus is a key cerebral invasion route for T cells after stroke.
    Acta Neuropathol 2017 Jul 31. Epub 2017 Jul 31.
    Institute for Stroke and Dementia Research, Klinikum der Universität München, Feodor-Lynen-Str. 17, 81377, Munich, Germany.
    Neuroinflammation contributes substantially to stroke pathophysiology. Cerebral invasion of peripheral leukocytes-particularly T cells-has been shown to be a key event promoting inflammatory tissue damage after stroke. While previous research has focused on the vascular invasion of T cells into the ischemic brain, the choroid plexus (ChP) as an alternative cerebral T-cell invasion route after stroke has not been investigated. Read More

    Muscle satellite cells are functionally impaired in myasthenia gravis: consequences on muscle regeneration.
    Acta Neuropathol 2017 Jul 29. Epub 2017 Jul 29.
    Sorbonne Universités, UPMC Université Paris 6, Paris, France.
    Myasthenia gravis (MG) is a neuromuscular disease caused in most cases by anti-acetyl-choline receptor (AChR) autoantibodies that impair neuromuscular signal transmission and affect skeletal muscle homeostasis. Myogenesis is carried out by muscle stem cells called satellite cells (SCs). However, myogenesis in MG had never been explored. Read More

    Persistent microglial activation and synaptic loss with behavioral abnormalities in mouse offspring exposed to CASPR2-antibodies in utero.
    Acta Neuropathol 2017 Jul 28. Epub 2017 Jul 28.
    Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
    Gestational transfer of maternal antibodies against fetal neuronal proteins may be relevant to some neurodevelopmental disorders, but until recently there were no proteins identified. We recently reported a fivefold increase in CASPR2-antibodies in mid-gestation sera from mothers of children with intellectual and motor disabilities. Here, we exposed mice in utero to purified IgG from patients with CASPR2-antibodies (CASPR2-IgGs) or from healthy controls (HC-IgGs). Read More

    Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome.
    Acta Neuropathol 2017 Jul 21. Epub 2017 Jul 21.
    Department of Pathology, University of Michigan, Ann Arbor, MI, 48104, USA.
    Posterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Read More

    Microglial-mediated PDGF-CC activation increases cerebrovascular permeability during ischemic stroke.
    Acta Neuropathol 2017 Jul 19. Epub 2017 Jul 19.
    Department of Physiology, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, BioPark-1, Room 211, 800 W. Baltimore Street, Baltimore, MD, 21201, USA.
    Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood-brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα). However, in vitro, activation of PDGF-CC by tPA is very inefficient and the mechanism of PDGF-CC activation in the NVU is not known. Read More

    α-Synuclein transfer between neurons and astrocytes indicates that astrocytes play a role in degradation rather than in spreading.
    Acta Neuropathol 2017 Jul 19. Epub 2017 Jul 19.
    Unité de Trafic Membranaire et Pathogénèse, Institut Pasteur, Paris, France.
    Recent evidence suggests that disease progression in Parkinson's disease (PD) could occur by the spreading of α-synuclein (α-syn) aggregates between neurons. Here we studied the role of astrocytes in the intercellular transfer and fate of α-syn fibrils, using in vitro and ex vivo models. α-Syn fibrils can be transferred to neighboring cells; however, the transfer efficiency changes depending on the cell types. Read More

    Medulloblastoma: experimental models and reality.
    Acta Neuropathol 2017 Jul 19. Epub 2017 Jul 19.
    Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
    Medulloblastoma is the most frequent malignant brain tumor in childhood, but it may also affect infants, adolescents, and young adults. Recent advances in the understanding of the disease have shed light on molecular and clinical heterogeneity, which is now reflected in the updated WHO classification of brain tumors. At the same time, it is well accepted that preclinical research and clinical trials have to be subgroup-specific. Read More

    Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood.
    Acta Neuropathol 2017 Jul 6. Epub 2017 Jul 6.
    Institute of Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
    Whereas microglia involvement in virtually all brain diseases is well accepted their role in the control of homeostasis in the central nervous system (CNS) is mainly thought to be the maintenance of neuronal function through the formation, refinement, and monitoring of synapses in both the developing and adult brain. Although the prenatal origin as well as the neuron-centered function of cortical microglia has recently been elucidated, much less is known about a distinct amoeboid microglia population formerly described as the "fountain of microglia" that appears only postnatally in myelinated regions such as corpus callosum and cerebellum. Using large-scale transcriptional profiling, fate mapping, and genetic targeting approaches, we identified a unique molecular signature of this microglia subset that arose from a CNS endogenous microglia pool independent from circulating myeloid cells. Read More

    Nogo-A antibodies enhance axonal repair and remyelination in neuro-inflammatory and demyelinating pathology.
    Acta Neuropathol 2017 Jun 23. Epub 2017 Jun 23.
    Brain Research Institute, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
    Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both characteristics may be influenced by the presence of inhibitory factors preventing myelin and neuronal repair. We investigated the potential of antibodies against Nogo-A, a well-known inhibitory protein for neuronal growth and plasticity, to enhance neuronal regeneration and remyelination in two animal models of multiple sclerosis. Read More

    Parietal white matter lesions in Alzheimer's disease are associated with cortical neurodegenerative pathology, but not with small vessel disease.
    Acta Neuropathol 2017 Jun 21. Epub 2017 Jun 21.
    Institute of Neuroscience, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
    Cerebral white matter lesions (WML) encompass axonal loss and demyelination, and the pathogenesis is assumed to be small vessel disease (SVD)-related ischemia. However, WML may also result from the activation of Wallerian degeneration as a consequence of cortical Alzheimer's disease (AD) pathology, i.e. Read More

    Same-day genomic and epigenomic diagnosis of brain tumors using real-time nanopore sequencing.
    Acta Neuropathol 2017 Jun 21. Epub 2017 Jun 21.
    Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière (ICM), Paris, France.
    Molecular classification of cancer has entered clinical routine to inform diagnosis, prognosis, and treatment decisions. At the same time, new tumor entities have been identified that cannot be defined histologically. For central nervous system tumors, the current World Health Organization classification explicitly demands molecular testing, e. Read More

    Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms.
    Acta Neuropathol 2017 Jun 21. Epub 2017 Jun 21.
    Department of Pediatrics/Child Neurology, VU University Medical Centre, Amsterdam Neuroscience, Amsterdam, The Netherlands.
    Leukodystrophies are genetically determined disorders characterized by the selective involvement of the central nervous system white matter. Onset may be at any age, from prenatal life to senescence. Many leukodystrophies are degenerative in nature, but some only impair white matter function. Read More

    Post-translational remodeling of ryanodine receptor induces calcium leak leading to Alzheimer's disease-like pathologies and cognitive deficits.
    Acta Neuropathol 2017 Jun 19. Epub 2017 Jun 19.
    Department of Physiology and Cellular Biophysics, Clyde and Helen Wu Center for Molecular Cardiology, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA.
    The mechanisms underlying ryanodine receptor (RyR) dysfunction associated with Alzheimer disease (AD) are still not well understood. Here, we show that neuronal RyR2 channels undergo post-translational remodeling (PKA phosphorylation, oxidation, and nitrosylation) in brains of AD patients, and in two murine models of AD (3 × Tg-AD, APP (+/-) /PS1 (+/-)). RyR2 is depleted of calstabin2 (KFBP12. Read More

    Myelin regulatory factor drives remyelination in multiple sclerosis.
    Acta Neuropathol 2017 Jun 19. Epub 2017 Jun 19.
    International Collaboration on Repair Discoveries (ICORD), Blusson Spinal Cord Centre, 818 West 10th Avenue, Vancouver, BC, V5Z 1M9, Canada.
    Remyelination is limited in the majority of multiple sclerosis (MS) lesions despite the presence of oligodendrocyte precursor cells (OPCs) in most lesions. This observation has led to the view that a failure of OPCs to fully differentiate underlies remyelination failure. OPC differentiation requires intricate transcriptional regulation, which may be disrupted in chronic MS lesions. Read More

    Phenotypic and functional characterization of T cells in white matter lesions of multiple sclerosis patients.
    Acta Neuropathol 2017 Jun 17. Epub 2017 Jun 17.
    Department of Viroscience, Erasmus MC, University Medical Center, Room Ee1720a, 's-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands.
    T cells are considered pivotal in the pathology of multiple sclerosis (MS), but their function and antigen specificity are unknown. To unravel the role of T cells in MS pathology, we performed a comprehensive analysis on T cells recovered from paired blood, cerebrospinal fluid (CSF), normal-appearing white matter (NAWM) and white matter lesions (WML) from 27 MS patients with advanced disease shortly after death. The differentiation status of T cells in these compartments was determined by ex vivo flow cytometry and immunohistochemistry. Read More

    IFN-β-induced reactive oxygen species and mitochondrial damage contribute to muscle impairment and inflammation maintenance in dermatomyositis.
    Acta Neuropathol 2017 Jun 16. Epub 2017 Jun 16.
    Institut de Physiologie EA 3072, Service de Physiologie et d'Explorations Fonctionnelles, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
    Dermatomyositis (DM) is an autoimmune disease associated with enhanced type I interferon (IFN) signalling in skeletal muscle, but the mechanisms underlying muscle dysfunction and inflammation perpetuation remain unknown. Transcriptomic analysis of early untreated DM muscles revealed that the main cluster of down-regulated genes was mitochondria-related. Histochemical, electron microscopy, and in situ oxygraphy analysis showed mitochondrial abnormalities, including increased reactive oxygen species (ROS) production and decreased respiration, which was correlated with low exercise capacities and a type I IFN signature. Read More

    The enteric nervous system is a potential autoimmune target in multiple sclerosis.
    Acta Neuropathol 2017 Aug 15;134(2):281-295. Epub 2017 Jun 15.
    Department of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
    Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) in young adults that has serious negative socioeconomic effects. In addition to symptoms caused by CNS pathology, the majority of MS patients frequently exhibit gastrointestinal dysfunction, which was previously either explained by the presence of spinal cord lesions or not directly linked to the autoimmune etiology of the disease. Here, we studied the enteric nervous system (ENS) in a B cell- and antibody-dependent mouse model of MS by immunohistochemistry and electron microscopy at different stages of the disease. Read More

    [F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging.
    Acta Neuropathol 2017 Jun 13. Epub 2017 Jun 13.
    MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA, USA.
    [F-18]-AV-1451, a PET tracer specifically developed to detect brain neurofibrillary tau pathology, has the potential to facilitate accurate diagnosis of Alzheimer's disease (AD), staging of brain tau burden and monitoring disease progression. Recent PET studies show that patients with mild cognitive impairment and AD dementia exhibit significantly higher in vivo [F-18]-AV-1451 retention than cognitively normal controls. Importantly, PET patterns of [F-18]-AV-1451 correlate well with disease severity and seem to match the predicted topographic Braak staging of neurofibrillary tangles (NFTs) in AD, although this awaits confirmation. Read More

    Deficiency of TYROBP, an adapter protein for TREM2 and CR3 receptors, is neuroprotective in a mouse model of early Alzheimer's pathology.
    Acta Neuropathol 2017 Jun 13. Epub 2017 Jun 13.
    Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
    Conventional genetic approaches and computational strategies have converged on immune-inflammatory pathways as key events in the pathogenesis of late onset sporadic Alzheimer's disease (LOAD). Mutations and/or differential expression of microglial specific receptors such as TREM2, CD33, and CR3 have been associated with strong increased risk for developing Alzheimer's disease (AD). DAP12 (DNAX-activating protein 12)/TYROBP, a molecule localized to microglia, is a direct partner/adapter for TREM2, CD33, and CR3. Read More

    Remodeling of heterochromatin structure slows neuropathological progression and prolongs survival in an animal model of Huntington's disease.
    Acta Neuropathol 2017 Jun 7. Epub 2017 Jun 7.
    VA Boston Healthcare System, Boston, MA, 02130, USA.
    Huntington's disease (HD) is an autosomal-dominant inherited neurological disorder caused by expanded CAG repeats in exon 1 of the Huntingtin (HTT) gene. Altered histone modifications and epigenetic mechanisms are closely associated with HD suggesting that transcriptional repression may play a pathogenic role. Epigenetic compounds have significant therapeutic effects in cellular and animal models of HD, but they have not been successful in clinical trials. Read More

    Autism spectrum disorder: neuropathology and animal models.
    Acta Neuropathol 2017 Jun 5. Epub 2017 Jun 5.
    Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, Box 1639, One Gustave L. Levy Place, New York, NY, 10029, USA.
    Autism spectrum disorder (ASD) has a major impact on the development and social integration of affected individuals and is the most heritable of psychiatric disorders. An increase in the incidence of ASD cases has prompted a surge in research efforts on the underlying neuropathologic processes. We present an overview of current findings in neuropathology studies of ASD using two investigational approaches, postmortem human brains and ASD animal models, and discuss the overlap, limitations, and significance of each. Read More

    Bystander mechanism for complement-initiated early oligodendrocyte injury in neuromyelitis optica.
    Acta Neuropathol 2017 Jul 31;134(1):35-44. Epub 2017 May 31.
    Departments of Medicine and Physiology, University of California, San Francisco, 1246 Health Sciences East Tower, San Francisco, CA, 94143-0521, USA.
    Neuromyelitis optica spectrum disorder (herein called NMO) is an autoimmune inflammatory disease of the central nervous system in which immunoglobulin G antibodies against astrocyte water channel aquaporin-4 (AQP4-IgG) cause demyelination and neurological deficit. Injury to oligodendrocytes, which do not express AQP4, links the initiating pathogenic event of AQP4-IgG binding to astrocyte AQP4 to demyelination. Here, we report evidence for a complement 'bystander mechanism' to account for early oligodendrocyte injury in NMO in which activated, soluble complement proteins following AQP4-IgG binding to astrocyte AQP4 result in deposition of the complement membrane attack complex (MAC) on nearby oligodendrocytes. Read More

    NG2 plays a role in neuroinflammation but is not expressed by immune cells.
    Acta Neuropathol 2017 Aug 31;134(2):325-327. Epub 2017 May 31.
    Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

    White matter injury in the preterm infant: pathology and mechanisms.
    Acta Neuropathol 2017 May 22. Epub 2017 May 22.
    Division of Pediatric Neuroscience, Departments of Pediatrics and Neurology, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Rd, Portland, OR, 97239-3098, USA.
    The human preterm brain is particularly susceptible to cerebral white matter injury (WMI) that disrupts the normal progression of developmental myelination. Advances in the care of preterm infants have resulted in a sustained reduction in the severity of WMI that has shifted from more severe focal necrotic lesions to milder diffuse WMI. Nevertheless, WMI remains a global health problem and the most common cause of chronic neurological morbidity from cerebral palsy and diverse neurobehavioral disabilities. Read More

    Amyotrophic lateral sclerosis-like superoxide dismutase 1 proteinopathy is associated with neuronal loss in Parkinson's disease brain.
    Acta Neuropathol 2017 Jul 19;134(1):113-127. Epub 2017 May 19.
    Discipline of Biomedical Science and Brain and Mind Centre, Sydney Medical School, The University of Sydney, Sydney, NSW, 2006, Australia.
    Neuronal loss in numerous neurodegenerative disorders has been linked to protein aggregation and oxidative stress. Emerging data regarding overlapping proteinopathy in traditionally distinct neurodegenerative diseases suggest that disease-modifying treatments targeting these pathological features may exhibit efficacy across multiple disorders. Here, we describe proteinopathy distinct from classic synucleinopathy, predominantly comprised of the anti-oxidant enzyme superoxide dismutase-1 (SOD1), in the Parkinson's disease brain. Read More

    Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins.
    Acta Neuropathol 2017 May 19. Epub 2017 May 19.
    Integrative Cell Biology Program, Loyola University Chicago, Maywood, IL, 60153, USA.
    Numerous pathological amyloid proteins spread from cell to cell during neurodegenerative disease, facilitating the propagation of cellular pathology and disease progression. Understanding the mechanism by which disease-associated amyloid protein assemblies enter target cells and induce cellular dysfunction is, therefore, key to understanding the progressive nature of such neurodegenerative diseases. In this study, we utilized an imaging-based assay to monitor the ability of disease-associated amyloid assemblies to rupture intracellular vesicles following endocytosis. Read More

    In-depth clinico-pathological examination of RNA foci in a large cohort of C9ORF72 expansion carriers.
    Acta Neuropathol 2017 Aug 15;134(2):255-269. Epub 2017 May 15.
    Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA.
    A growing body of evidence suggests that a loss of chromosome 9 open reading frame 72 (C9ORF72) expression, formation of dipeptide-repeat proteins, and generation of RNA foci contribute to disease pathogenesis in amyotrophic lateral sclerosis and frontotemporal dementia. Although the levels of C9ORF72 transcripts and dipeptide-repeat proteins have already been examined thoroughly, much remains unknown about the role of RNA foci in C9ORF72-linked diseases. As such, we performed a comprehensive RNA foci study in an extensive pathological cohort of C9ORF72 expansion carriers (n = 63). Read More

    HSPB8 haploinsufficiency causes dominant adult-onset axial and distal myopathy.
    Acta Neuropathol 2017 Jul 13;134(1):163-165. Epub 2017 May 13.
    Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Illkirch, France.

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