Distinct conformers of transmissible misfolded SOD1 distinguish human SOD1-FALS from other forms of familial and sporadic ALS.

Abstract:

:Evidence of misfolded wild-type superoxide dismutase 1 (SOD1) has been detected in spinal cords of sporadic ALS (sALS) patients, suggesting an etiological relationship to SOD1-associated familial ALS (fALS). Given that there are currently a number of promising therapies under development that target SOD1, it is of critical importance to better understand the role of misfolded SOD1 in sALS. We previously demonstrated the permissiveness of the G85R-SOD1:YFP mouse model for MND induction following injection with tissue homogenates from paralyzed transgenic mice expressing SOD1 mutations. This prompted us to examine whether WT SOD1 can self-propagate misfolding of the G85R-SOD1:YFP protein akin to what has been observed with mutant SOD1. Using the G85R-SOD1:YFP mice, we demonstrate that misfolded conformers of recombinant WT SOD1, produced in vitro, induce MND with a distinct inclusion pathology. Furthermore, the distinct pathology remains upon successive passages in the G85R-SOD1:YFP mice, strongly supporting the notion for conformation-dependent templated propagation and SOD1 strains. To determine the presence of a similar misfolded WT SOD1 conformer in sALS tissue, we screened homogenates from patients diagnosed with sALS, fALS, and non-ALS disease in an organotypic spinal cord slice culture assay. Slice cultures from G85R-SOD1:YFP mice exposed to spinal homogenates from patients diagnosed with ALS caused by the A4V mutation in SOD1 developed robust inclusion pathology, whereas spinal homogenates from more than 30 sALS cases and various controls failed. These findings suggest that mutant SOD1 has prion-like attributes that do not extend to SOD1 in sALS tissues.

journal_name

Acta Neuropathol

journal_title

Acta neuropathologica

authors

Ayers JI,Diamond J,Sari A,Fromholt S,Galaleldeen A,Ostrow LW,Glass JD,Hart PJ,Borchelt DR

doi

10.1007/s00401-016-1623-4

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

827-840

issue

6

eissn

0001-6322

issn

1432-0533

pii

10.1007/s00401-016-1623-4

journal_volume

132

pub_type

杂志文章
  • Persistent eIF2alpha(P) is colocalized with cytoplasmic cytochrome c in vulnerable hippocampal neurons after 4 hours of reperfusion following 10-minute complete brain ischemia.

    abstract::Upon brain reperfusion following ischemia, there is widespread inhibition of neuronal protein synthesis that is due to phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha), which persists in selectively vulnerable neurons (SVNs) destined to die. Other investigators have shown that expression of mutant eI...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-003-0693-2

    authors: Page AB,Owen CR,Kumar R,Miller JM,Rafols JA,White BC,DeGracia DJ,Krause GS

    更新日期:2003-07-01 00:00:00

  • Corticobasal degeneration with focal, massive tau accumulation in the subcortical white matter astrocytes.

    abstract::We report two sporadic cases of tauopathy with unusual neuropathological features. The ages of the patients at death were 86 and 74 years, and the disease durations were 4 and 3 years, respectively. The former patient showed progressive dementia and amyotrophy (autopsy revealed that severe cervical spondylosis was res...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-006-0093-5

    authors: Sakai K,Piao YS,Kikugawa K,Ohara S,Hasegawa M,Takano H,Fukase M,Nishizawa M,Kakita A,Takahashi H

    更新日期:2006-09-01 00:00:00

  • Fine structure of a cerebellar "fibroma".

    abstract::The fine structure of an intracerebellar "fibroma" has been examined. The tumor consists of irregularly-shaped cells connected by well developed junctional complexes. Unusual, fenestrated capillaries with extremely narrow and irregular lumens are frequent. Collagen fibers are not common but the wide extracellular spac...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00696567

    authors: Hirano A,Llena JF,Chung HD

    更新日期:1975-08-27 00:00:00

  • Peripheral nerve findings in hereditary coproporphyria. Light and ultrastructural studies in two sural nerve biopsies.

    abstract::In spite of several cases reported in the literature, the exact pathogenetic mechanism of neuropathic changes in porphyric neuropathy remains uncertain. Various authors have ascribed the neuropathologic findings to either a dying-back axonal degeneration or segmental demyelination. In recent years, the hypothesis of a...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00697191

    authors: Di Trapani G,Casali C,Tonali P,Topi GC

    更新日期:1984-01-01 00:00:00

  • Long-term proteasomal inhibition in transgenic mice by UBB(+1) expression results in dysfunction of central respiration control reminiscent of brainstem neuropathology in Alzheimer patients.

    abstract::Aging and neurodegeneration are often accompanied by a functionally impaired ubiquitin-proteasome system (UPS). In tauopathies and polyglutamine diseases, a mutant form of ubiquitin B (UBB(+1)) accumulates in disease-specific aggregates. UBB(+1) mRNA is generated at low levels in vivo during transcription from the ubi...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-012-1003-7

    authors: Irmler M,Gentier RJ,Dennissen FJ,Schulz H,Bolle I,Hölter SM,Kallnik M,Cheng JJ,Klingenspor M,Rozman J,Ehrhardt N,Hermes DJ,Gailus-Durner V,Fuchs H,Hrabě de Angelis M,Meyer HE,Hopkins DA,Van Leeuwen FW,Beckers J

    更新日期:2012-08-01 00:00:00

  • Androgen-dependent impairment of myogenesis in spinal and bulbar muscular atrophy.

    abstract::Spinal and bulbar muscular atrophy (SBMA) is an inherited neuromuscular disease caused by expansion of a polyglutamine (polyQ) tract in the androgen receptor (AR). SBMA is triggered by the interaction between polyQ-AR and its natural ligands, testosterone and dihydrotestosterone (DHT). SBMA is characterized by the los...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-013-1122-9

    authors: Malena A,Pennuto M,Tezze C,Querin G,D'Ascenzo C,Silani V,Cenacchi G,Scaramozza A,Romito S,Morandi L,Pegoraro E,Russell AP,Sorarù G,Vergani L

    更新日期:2013-07-01 00:00:00

  • Congenital lead encephalopathy in monkeys.

    abstract::Thirty-one squirrel monkey fetuses were exposed to lead acetate given to the mothers perorally during the last three-fourths or two-thirds of pregnancy. The mean maternal blood lead concentration of the group was 37 micrograms/100 ml and the individual means ranged from 22-82 micrograms/100 ml. Examination of the cent...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00687421

    authors: Lögdberg B,Brun A,Berlin M,Schütz A

    更新日期:1988-01-01 00:00:00

  • Curly fibers are tau-positive strands in the pre- and post-synaptic neurites, consisting of paired helical filaments: observations by the freeze-etch and replica method.

    abstract::The ultrastructure of the curly fibers was examined by the transmission and immunoelectron microscopy as well as by the rapid-freeze, deep-etch and replica method. The curly fibers consisted mainly of paired helical filaments (PHF) in the neuropils, both pre- and post-synaptic. On the deep-etch replicas, PHF in the ne...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00334498

    authors: Ohtsubo K,Izumiyama N,Kuzuhara S,Mori H,Shimada H

    更新日期:1990-01-01 00:00:00

  • Neurologic complications of Hodgkin's disease. Choroid plexus involvement.

    abstract::Involvement of the choroid plexus by lymphoma (Hodgkin) is a hitherto undescribed complication. We report herein the case of a 49-year-old man who developed, shortly before death, neurologic symptoms seemingly related to extensive involvement of choroid plexus and surrounding ventricular structures by lymphoma (Hodgki...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00692063

    authors: Sanchez JE,Garcia JH,Kwee H

    更新日期:1977-02-28 00:00:00

  • Phagocytosis of apoptotic lymphocytes by oligodendrocytes in experimental autoimmune encephalomyelitis.

    abstract::The alterations in oligodendrocytes in myelin basic protein-induced acute experimental autoimmune encephalomyelitis (EAE) in the Lewis rat were studied using the technique of pre-embedding immunolabelling with the Rip monoclonal antibody, which specifically labels the cytoplasm of the cell bodies and processes of olig...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010050763

    authors: Nguyen KB,Pender MP

    更新日期:1998-01-01 00:00:00

  • Myopathy in Marinesco-Sjögren syndrome links endoplasmic reticulum chaperone dysfunction to nuclear envelope pathology.

    abstract::Marinesco-Sjögren syndrome (MSS) features cerebellar ataxia, mental retardation, cataracts, and progressive vacuolar myopathy with peculiar myonuclear alterations. Most MSS patients carry homozygous or compound heterozygous SIL1 mutations. SIL1 is a nucleotide exchange factor for the endoplasmic reticulum resident cha...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-013-1224-4

    authors: Roos A,Buchkremer S,Kollipara L,Labisch T,Gatz C,Zitzelsberger M,Brauers E,Nolte K,Schröder JM,Kirschner J,Jesse CM,Goebel HH,Goswami A,Zimmermann R,Zahedi RP,Senderek J,Weis J

    更新日期:2014-05-01 00:00:00

  • Presence of non-fibrillar amyloid beta protein in skin biopsies of Alzheimer's disease (AD), Down's syndrome and non-AD normal persons.

    abstract::A total of 66 skin biopsies from persons with Alzheimer's disease (AD) or Down's syndrome (DS) and from persons without AD were used in this study. The age range was from 7 to 89 years. Positive immunoreactivity of skin biopsies to monoclonal antibody 4G8, which is reactive to amino acid residue 17-24 of synthetic amy...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00293394

    authors: Wen GY,Wisniewski HM,Blondal H,Benedikz E,Frey H,Pirttila T,Rudelli R,Kim KS

    更新日期:1994-01-01 00:00:00

  • Splanchnic preganglionic neurons in man. I. Morphometry of preganglionic cytons.

    abstract::The thoracic sympathetic preganglionic outflow is important in the maintenance of postural normotension in man. Normative data on the intermediolateral column (ILC) neuron cell bodies is lacking. Counts and measurements on the right ILC cytons have been performed on the T6, T7 and T8 segments of 12 spinal cords of man...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00688573

    authors: Low PA,Okazaki H,Dyck PJ

    更新日期:1977-09-26 00:00:00

  • Tumour necrosis factor-mediated cell death pathways do not contribute to muscle fibre death in dystrophinopathies.

    abstract::There is evidence that apoptotic cell death mechanisms contribute to muscle fibre loss in dystrophinopathies, but little knowledge about the activators of the final degrading caspase cascade in muscle fibre apoptosis. As mitochondria-related activation of this caspase cascade, through e.g. APAF-1, could not be proven ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-004-0934-z

    authors: Tews DS

    更新日期:2005-02-01 00:00:00

  • Plaque-like structures and arteriosclerotic changes in "diffuse neurofibrillary tangles with calcification" (DNTC).

    abstract::"Diffuse neurofibrillary tangles with calcification" (DNTC) is a rare form of slowly progressive dementia characterized by temporal or fronto-temporal atrophy with neuronal loss and astrocytosis, neurofibrillary tangles and Fahr-type calcification, but no senile plaques in the cerebral cortex. In patients with DNTC, w...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s004010100411

    authors: Terada S,Ishizu H,Tanabe Y,Takehisa Y,Haraguchi T,Hamaya K,Nose S,Sudo K,Kuroda S

    更新日期:2001-12-01 00:00:00

  • Mucopolysaccharidosis type I, II, IIIA and V. Pathological and biochemical abnormalities in the neural and mesenchymal elements of the brain.

    abstract::Histochemical and electron microscopic studies of the brains inclusive of the leptomeninges containing large blood vessels from 7 patients with mucopolysaccharidosis (MPS) I, II, IIIA and V showed marked increase in mesenchymal elements and the generalized presence of characteristic lesions around cerebral veins and a...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00690379

    authors: Dekaban AS,Constantopoulos G

    更新日期:1977-07-15 00:00:00

  • Megacolon in third-phase malrotation with delayed migration and degeneration of intramural ganglionic cells and nerves.

    abstract::A woman of 36 was admitted to hospital because of griping abdominal pain which occurred especially during the night when turning in bed. She had a history of constipation and bloating since birth. Irrigoscopy revealed megacolon extending from the middle of the transverse colon to the rectum. A rectal biopsy excluded H...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00688193

    authors: Lassmann G

    更新日期:1987-01-01 00:00:00

  • Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine labeling, and nucleolar organizer region counts.

    abstract::The growth potential of 65 pituitary adenomas was determined by histochemical analysis with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine (BrdUdR) labeling, and counts of argyrophilic nucleolar organizer regions (Ag-NORs). The mean proliferating cell indices (PCIs) determined by Ki-67 an...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00311392

    authors: Shibuya M,Saito F,Miwa T,Davis RL,Wilson CB,Hoshino T

    更新日期:1992-01-01 00:00:00

  • Regional and cellular pathology in frontotemporal dementia: relationship to stage of disease in cases with and without Pick bodies.

    abstract::Frontotemporal dementia (FTD) is a prevalent neurodegenerative disease of heterogeneous histopathology. Neuropathological subtypes are identified on the basis of the presence or absence of tau- or ubiquitin-positive neuronal inclusions. Our recent work has established four disease stages that are independent of neurop...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-004-0917-0

    authors: Kersaitis C,Halliday GM,Kril JJ

    更新日期:2004-12-01 00:00:00

  • Consensus classification of human prion disease histotypes allows reliable identification of molecular subtypes: an inter-rater study among surveillance centres in Europe and USA.

    abstract::The current classification of human sporadic prion diseases recognizes six major phenotypic subtypes with distinctive clinicopathological features, which largely correlate at the molecular level with the genotype at the polymorphic codon 129 (methionine, M, or valine, V) in the prion protein gene and with the size of ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-012-1002-8

    authors: Parchi P,de Boni L,Saverioni D,Cohen ML,Ferrer I,Gambetti P,Gelpi E,Giaccone G,Hauw JJ,Höftberger R,Ironside JW,Jansen C,Kovacs GG,Rozemuller A,Seilhean D,Tagliavini F,Giese A,Kretzschmar HA

    更新日期:2012-10-01 00:00:00

  • Alterations of ubiquitin immunoreactivity in the hippocampal formation after perforant pathway lesion.

    abstract::Immunohistochemical techniques were employed to examine the changes in free ubiquitin within the hippocampus 1, 3, 7, 14, and 30 days after a unilateral perforant pathway lesion occurred in the rat brain. Immunoreactivity for ubiquitin was remarkably decreased in the cell body and proximal dendrites of neurons through...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-001-0489-1

    authors: Mizukami K,Ishikawa M,Iwakiri M,Hidaka S,Kato N,Asada T

    更新日期:2002-05-01 00:00:00

  • Extracellular edema and glial response to it in the cerebellum of suckling rats with low-dose lead encephalopathy. An electron microscopic and immunohistochemical study.

    abstract::Newborn rats were exposed to daily intraperitoneal injections of 10 mg lead nitrate per kg body weight for the first 15 postnatal days. The growth and mortality of the lead-exposed animals did not differ from their control litter-mates, injected with vehicle only. In our previous studies, focal hemorrhages and spongy ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00687071

    authors: Sundström R,Kalimo H

    更新日期:1987-01-01 00:00:00

  • Evaluation of CD33 as a genetic risk factor for Alzheimer's disease.

    abstract::In 2011, genome-wide association studies implicated a polymorphism near CD33 as a genetic risk factor for Alzheimer's disease. This finding sparked interest in this member of the sialic acid-binding immunoglobulin-type lectin family which is linked to innate immunity. Subsequent studies found that CD33 is expressed in...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章,评审

    doi:10.1007/s00401-019-02000-4

    authors: Estus S,Shaw BC,Devanney N,Katsumata Y,Press EE,Fardo DW

    更新日期:2019-08-01 00:00:00

  • Primary leptomeningeal glioma: ultrastructural and laminin immunohistochemical studies.

    abstract::We studied a case of primary leptomeningeal glioma (PLG) on the left parietal lobe of a 74-year-old woman and compared the tissue with heterotopic glial tissue from another case. The PLG tumor consisted of spindle-shaped cells with marked nuclear atypism, which tended to be arranged in a fascicular pattern, and the ma...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00310033

    authors: Kakita A,Wakabayashi K,Takahashi H,Ohama E,Ikuta F,Tokiguchi S

    更新日期:1992-01-01 00:00:00

  • A new form of ovine GM1-gangliosidosis.

    abstract::Neurological signs were observed in 3 lambs at approximately 1 month of age, in a flock of 1 ram and 29 ewes with 43 lambs. Deterioration occurred such that the lambs had either died or been killed by 4 months of age. Necropsies of two of these lambs revealed a diffuse encephalopathy in which the most prominent featur...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00309632

    authors: Skelly BJ,Jeffrey M,Franklin RJ,Winchester BG

    更新日期:1995-01-01 00:00:00

  • Neuronal autophagy in experimental Creutzfeldt-Jakob's disease.

    abstract::We report an experimental model of Creutzfeldt-Jakob's disease (CJD) in mice leading to the formation of giant autophagic vacuoles (AV) in neurons of the cerebral cortex. These AV appear at the end of the incubation period (4-6 months postinoculation), together with spongy changes and clinical symptoms. Autophagy, a p...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/BF00688178

    authors: Boellaard JW,Schlote W,Tateishi J

    更新日期:1989-01-01 00:00:00

  • Aristaless-related homeobox gene disruption leads to abnormal distribution of GABAergic interneurons in human neocortex: evidence based on a case of X-linked lissencephaly with abnormal genitalia (XLAG).

    abstract::X-linked lissencephaly with abnormal genitalia (XLAG) is a rare disorder caused by mutations in the aristaless-related homeobox (ARX) gene, located on Xp22.13. Arx-null mice show loss of tangential migration of GABAergic interneurons, presumably being related to caudal ganglionic eminence tangential migration. In the ...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-008-0382-2

    authors: Okazaki S,Ohsawa M,Kuki I,Kawawaki H,Koriyama T,Ri S,Ichiba H,Hai E,Inoue T,Nakamura H,Goto Y,Tomiwa K,Yamano T,Kitamura K,Itoh M

    更新日期:2008-10-01 00:00:00

  • Prevalence of cerebrovascular lesions in Parkinson's disease. A postmortem study.

    abstract::Data on the relationship between Parkinson's disease (PD) and stroke have been conflicting, some studies showing a reduced risk of stroke during life, and others indicating an increased risk of stroke-related death. Consecutive cases (n=617) of autopsy-proven idiopathic PD (Lewy body disease of the brain stem type) an...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-003-0676-3

    authors: Jellinger KA

    更新日期:2003-05-01 00:00:00

  • Endogenous oligodendroglial alpha-synuclein and TPPP/p25α orchestrate alpha-synuclein pathology in experimental multiple system atrophy models.

    abstract::Multiple system atrophy (MSA) is characterized by the presence of distinctive glial cytoplasmic inclusions (GCIs) within oligodendrocytes that contain the neuronal protein alpha-synuclein (aSyn) and the oligodendroglia-specific phosphoprotein TPPP/p25α. However, the role of oligodendroglial aSyn and p25α in the format...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-019-02014-y

    authors: Mavroeidi P,Arvanitaki F,Karakitsou AK,Vetsi M,Kloukina I,Zweckstetter M,Giller K,Becker S,Sorrentino ZA,Giasson BI,Jensen PH,Stefanis L,Xilouri M

    更新日期:2019-09-01 00:00:00

  • Active, phosphorylation-dependent MAP kinases, MAPK/ERK, SAPK/JNK and p38, and specific transcription factor substrates are differentially expressed following systemic administration of kainic acid to the adult rat.

    abstract::Excitotoxicity is considered a major cell death inductor in neurodegeneration. Yet the mechanisms involved in cell death and cell survival following excitotoxic insults are poorly understood. Expression of active, phosphorylation-dependent mitogen-activated extracellular signal-regulated kinases (MAPK/ERKs), stress-ac...

    journal_title:Acta neuropathologica

    pub_type: 杂志文章

    doi:10.1007/s00401-001-0481-9

    authors: Ferrer I,Blanco R,Carmona M,Puig B,Domínguez I,Viñals F

    更新日期:2002-04-01 00:00:00