Evidence for the Deregulation of Protein Turnover Pathways in Atm-Deficient Mouse Cerebellum: An Organotypic Study.

Abstract:

:Interferon-stimulated gene 15 (ISG15), an antagonist of the ubiquitin pathway, is elevated in cells and brain tissues obtained from ataxia telangiectasia (A-T) patients. Previous studies reveal that an elevated ISG15 pathway inhibits ubiquitin-dependent protein degradation, leading to activation of basal autophagy as a compensatory mechanism for protein turnover in A-T cells. Also, genotoxic stress (ultraviolet [UV] radiation) deregulates autophagy and induces aberrant degradation of ubiquitylated proteins in A-T cells. In the current study, we show that, as in A-T cells, ISG15 protein expression is elevated in cerebellums and various other tissues obtained from Atm-compromised mice in an Atm-allele-dependent manner (Atm+/+ < Atm+/- < Atm-/-). Notably, in cerebellums, the brain part primarily affected in A-T, levels of ISG15 were significantly greater (3-fold higher) than cerebrums obtained from the same set of mice. Moreover, as in A-T cell culture, UV induces aberrant degradation of ubiquitylated proteins and autophagy in Atm-deficient, but not in Atm-proficient, cerebellar brain slices grown in culture. Thus, the ex vivo organotypic A-T mouse brain culture model mimics that of an A-T human cell culture model and could be useful for studying the role of ISG15-dependent proteinopathy in cerebellar neurodegeneration, a hallmark of A-T in humans.

authors

Kim CD,Reed RE,Juncker MA,Fang Z,Desai SD

doi

10.1093/jnen/nlx038

subject

Has Abstract

pub_date

2017-07-01 00:00:00

pages

578-584

issue

7

eissn

0022-3069

issn

1554-6578

pii

3850161

journal_volume

76

pub_type

杂志文章
  • Altered balance of proteolytic isoforms of pro-brain-derived neurotrophic factor in autism.

    abstract::Defects in synaptic development and plasticity may lead to autism. Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptogenesis and synaptic plasticity. BDNF is synthesized as a precursor, pro-BDNF, which can be processed into either a truncated form or into mature BDNF. Previous studies reported i...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e31824b27e4

    authors: Garcia KL,Yu G,Nicolini C,Michalski B,Garzon DJ,Chiu VS,Tongiorgi E,Szatmari P,Fahnestock M

    更新日期:2012-04-01 00:00:00

  • A familial form of pallidoluysionigral degeneration and amyotrophic lateral sclerosis with divergent clinical presentations.

    abstract::We describe a family with a rapidly progressive neurodegenerative disorder characterized by amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) but with unusual neuropathologic features that include pallidoluysionigral degeneration. The proband presented with primary progressive aphasia that evolved ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/nen.0b013e318093f40d

    authors: Portera-Cailliau C,Russ C,Brown RH Jr,Budson AE,Vonsattel JP,Folkerth RD,Corbo JC

    更新日期:2007-07-01 00:00:00

  • Development and characterization of a novel human in vitro blood-nerve barrier model using primary endoneurial endothelial cells.

    abstract::There are phenotypic and functional differences between vascular endothelium from different tissues and between microvascular and macrovascular endothelial cells (ECs) from the same tissue. Relatively little is known about the human blood-nerve barrier (BNB). We report the development of an in vitro BNB model using pr...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3181c84a9a

    authors: Yosef N,Xia RH,Ubogu EE

    更新日期:2010-01-01 00:00:00

  • Progressive demyelination and reparative phenomena in chronic experimental allergic encephalomyelitis.

    abstract::Chronic experimental allergic encephalomyelitis (EAE), produced in inbred guinea pigs given a single inoculation during the juvenile period with isologous spinal cord in complete Freund's adjuvant, has been studied by light and electron microscopy. Most animals showed a delayed onset of nurologic signs from 12 to 68 w...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-197505000-00001

    authors: Snyder DH,Valsamis MP,Stone SH,Raine CS

    更新日期:1975-05-01 00:00:00

  • BRAF alterations in primary glial and glioneuronal neoplasms of the central nervous system with identification of 2 novel KIAA1549:BRAF fusion variants.

    abstract::Recent studies highlight the importance of BRAF alterations resulting in mitogen activated protein kinase (MAK/ERK) pathway activation in low-grade CNS tumors. We studied 106 low-grade CNS neoplasms in a cohort of primarily pediatric patients to identify the prevalence and clinicopathologic significance of these alter...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e31823f2cb0

    authors: Lin A,Rodriguez FJ,Karajannis MA,Williams SC,Legault G,Zagzag D,Burger PC,Allen JC,Eberhart CG,Bar EE

    更新日期:2012-01-01 00:00:00

  • Molecular regulation of acute ethanol-induced neuron apoptosis.

    abstract::Ethanol is a potent neurotoxin particularly for the developing nervous system. Intrauterine exposure to ethanol during the last trimester of human gestation can produce a broad spectrum of neuropathologic consequences. This period of human brain development is roughly equivalent to the first week of rodent postnatal l...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/64.6.490

    authors: Nowoslawski L,Klocke BJ,Roth KA

    更新日期:2005-06-01 00:00:00

  • Atypical progressive supranuclear palsy with corticospinal tract degeneration.

    abstract::Progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), sporadic multisystem tauopathy, and some forms of frontotemporal dementia with Parkinsonism linked to chromosome 17 are characterized by neuronal and glial lesions accumulating tau protein containing 4 conserved repeats in microtubule-binding domai...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/01.jnen.0000218446.38158.61

    authors: Josephs KA,Katsuse O,Beccano-Kelly DA,Lin WL,Uitti RJ,Fujino Y,Boeve BF,Hutton ML,Baker MC,Dickson DW

    更新日期:2006-04-01 00:00:00

  • Abnormal accumulation of tTGase products in muscle and erythrocytes of chorea-acanthocytosis patients.

    abstract::Chorea-Acanthocytosis (CHAC) is an autosomal recessive disease characterized by neurodegeneration and acanthocytosis. Enhanced creatine kinase concentration is a constant feature of the condition. The mechanism underlying CHAC is unknown. However, acanthocytosis and enhanced creatine kinase suggest a protein defect th...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/61.10.841

    authors: Melone MA,Di Fede G,Peluso G,Lus G,Di Iorio G,Sampaolo S,Capasso A,Gentile V,Cotrufo R

    更新日期:2002-10-01 00:00:00

  • Characterization of the early neuroinflammation after spinal cord injury in mice.

    abstract::The occurrence of neuroinflammation after spinal cord injury (SCI) is well established, but its function is debated, with both beneficial and detrimental consequences ascribed. A discriminate of the role of neuroinflammation may be the time period after SCI, and there is evidence to favor early neuroinflammation being...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/01.jnen.0000248552.07338.7f

    authors: Rice T,Larsen J,Rivest S,Yong VW

    更新日期:2007-03-01 00:00:00

  • Stereological analysis of cerebral atrophy in human immunodeficiency virus-associated dementia.

    abstract::Brain atrophy is a common finding in patients with AIDS, but the relationship of atrophy to HIV-associated dementia is unclear. We used unbiased, stereological methods on postmortem brain specimens to estimate volumes of different brain regions in patients prospectively diagnosed with and without HIV-associated dement...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:

    authors: Subbiah P,Mouton P,Fedor H,McArthur JC,Glass JD

    更新日期:1996-10-01 00:00:00

  • Reliability of differential PCR for the detection of EGFR and MDM2 gene amplification in DNA extracted from FFPE glioma tissue.

    abstract::A series of 43 human gliomas, consisting of 30 glioblastomas, 7 anaplastic astrocytomas, 3 low grade astrocytomas, 2 ependymomas, and 1 oligodendroglioma, was studied for amplification of the epidermal growth factor receptor (EGFR) and mouse double minute 2 (MDM2) genes. DNA extracted from formalin-fixed, paraffin-emb...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199501000-00007

    authors: Hunter SB,Abbott K,Varma VA,Olson JJ,Barnett DW,James CD

    更新日期:1995-01-01 00:00:00

  • Axotomized motoneurons can be rescued from cell death by peripheral nerve grafts: the effect of donor age.

    abstract::Injury to neonatal nerves, unlike adult nerves, results in poor regeneration and extensive motoneuron death. We examined whether exposure to a more mature nerve environment could rescue axotomized motoneurons following neonatal injury. The sciatic nerve in 1 hindlimb of 3-day-old (P3) rats was transected and the cut e...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/62.1.75

    authors: Low HL,Nogradi A,Vrbová G,Greensmith L

    更新日期:2003-01-01 00:00:00

  • Chronic prenatal exposure to carbon monoxide results in a reduction in tyrosine hydroxylase-immunoreactivity and an increase in choline acetyltransferase-immunoreactivity in the fetal medulla: implications for Sudden Infant Death Syndrome.

    abstract::Maternal cigarette smoking during pregnancy is associated with a significantly increased risk of Sudden Infant Death Syndrome (SIDS). This study investigated the effects of prenatal exposure to carbon monoxide (CO), a major component of cigarette smoke, on the neuroglial and neurochemical development of the medulla in...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/59.3.218

    authors: Tolcos M,McGregor H,Walker D,Rees S

    更新日期:2000-03-01 00:00:00

  • Quantitative Assessment of Pathological Tau Burden in Essential Tremor: A Postmortem Study.

    abstract::Essential tremor (ET) patients develop more cognitive impairment and dementia than controls, although there are surprisingly few data on the neuropathological basis for cognitive changes in ET. In this postmortem study, we assessed tau and other pathologies in 26 ET cases and 73 controls (non-ET) (1:3 matching). The m...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nly104

    authors: Farrell K,Cosentino S,Iida MA,Chapman S,Bennett DA,Faust PL,Louis ED,Crary JF

    更新日期:2019-01-01 00:00:00

  • Intermediate filaments in meningiomas.

    abstract::The presence of intermediate filaments (IF) (diameter 10 nm) is a characteristic electron microscopic finding in the cytoplasm of meningioma cells. To identify these IF, immunohistochemical staining for cytokeratins and vimentin and two-dimensional (2-D) gel electrophoresis followed by immunoblot analysis were applied...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198511000-00007

    authors: Halliday WC,Yeger H,Duwe GF,Phillips MJ

    更新日期:1985-11-01 00:00:00

  • Expression of Mutant Ubiquitin and Proteostasis Impairment in Kii Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex Brains.

    abstract::Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a progressive neurodegenerative disorder that is endemic to the Kii peninsula of Japan. The disorder is clinically characterized by a variable combination of parkinsonism, dementia, and motor neuron symptoms. Despite extensive investigations,...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nlaa056

    authors: Verheijen BM,Morimoto S,Sasaki R,Oyanagi K,Kokubo Y,Kuzuhara S,van Leeuwen FW

    更新日期:2020-08-01 00:00:00

  • Neuroinflammatory signals in Alzheimer disease and APP/PS1 transgenic mice: correlations with plaques, tangles, and oligomeric species.

    abstract::To understand neuroinflammation-related gene regulation during normal aging and in sporadic Alzheimer disease (sAD), we performed functional genomics analysis and analyzed messenger RNA (mRNA) expression by quantitative reverse transcription-polymerase chain reaction of 22 genes involved in neuroinflammation-like resp...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0000000000000176

    authors: López-González I,Schlüter A,Aso E,Garcia-Esparcia P,Ansoleaga B,LLorens F,Carmona M,Moreno J,Fuso A,Portero-Otin M,Pamplona R,Pujol A,Ferrer I

    更新日期:2015-04-01 00:00:00

  • Glutamate transporter alterations in Alzheimer disease are possibly associated with abnormal APP expression.

    abstract::Recent studies have shown that deficient functioning of glutamate transporters (GTs) in Alzheimer disease (AD) might lead to neurodegeneration. The main objectives of the present study were to determine which GT subtype is most affected in AD and to asses to what extent altered GT function is associated with abnormal ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199708000-00008

    authors: Li S,Mallory M,Alford M,Tanaka S,Masliah E

    更新日期:1997-08-01 00:00:00

  • Lewy body pathology in normal elderly subjects.

    abstract::Lewy bodies and Lewy neurites are the hallmark neuropathologic findings in Parkinson disease, Parkinson disease with dementia, dementia with Lewy bodies, and other alpha-synucleinopathies. They have also been described in the brains of normal older individuals and referred to as incidental Lewy body disease. The purpo...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3181ac10a7

    authors: Markesbery WR,Jicha GA,Liu H,Schmitt FA

    更新日期:2009-07-01 00:00:00

  • Axonal dystrophy in the gracile nucleus in congenital biliary atresia and cystic fibrosis (mucoviscidosis): beneficial effect of vitamin E therapy.

    abstract::In 63 patients with malabsorption syndromes, 16 with congenital biliary atresia (BA) and 47 with cystic fibrosis (CF), axonal dystrophy in the gracile nucleus (ADG) was studied. Of the 16 patients with BA, ADG of considerable severity was observed in all 10 over one year of age. Of the 47 patients with CF, it was obse...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198009000-00007

    authors: Sung JH,Park SH,Mastri AR,Warwick WJ

    更新日期:1980-09-01 00:00:00

  • Growth inhibition of cultured human glioma cells by beta-interferon is not dependent on changes in ganglioside composition.

    abstract::This investigation tested the hypothesis that the growth inhibiting effects of human beta-interferon on cultured human glioma cells involves changes in the ganglioside composition of these cells. Four cell lines derived from human malignant gliomas (12-18, U-251 MG, I29-A, 7-24) and two lines from human fetal brain (C...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198803000-00004

    authors: Yates AJ,Markowitz DL,Stephens RE,Pearl DK,Whisler RL

    更新日期:1988-03-01 00:00:00

  • Third ventricular chordoid glioma: a distinct clinicopathologic entity.

    abstract::We have encountered a series of 8 third ventricular neoplasms with a distinctive chordoid appearance that appear to represent a clinicopathologic entity. The tumors occurred in 7 females and 1 male, ranging in age from 31 to 70 years. In all cases, imaging studies showed a large well-circumscribed third ventricular ma...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199803000-00009

    authors: Brat DJ,Scheithauer BW,Staugaitis SM,Cortez SC,Brecher K,Burger PC

    更新日期:1998-03-01 00:00:00

  • Expression of chemokine receptors CCR1 and CCR5 reflects differential activation of mononuclear phagocytes in pattern II and pattern III multiple sclerosis lesions.

    abstract::Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the CNS. A recent study identified 4 patterns of demyelination in active MS lesions. The characteristics of pattern II lesions suggested a primary inflammatory mechanism of myelin injury, while pattern III lesions showed features consistent with dyin...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/63.3.262

    authors: Mahad DJ,Trebst C,Kivisäkk P,Staugaitis SM,Tucky B,Wei T,Lucchinetti CF,Lassmann H,Ransohoff RM

    更新日期:2004-03-01 00:00:00

  • Membranous bodies in the cerebral cortex of aging rats: an electron microscope study.

    abstract::Large complex membranous bodies are described in the cerebral cortex of adult rats. Although these bodies are not very prevalent, they appear with increasing frequency as the age of the animal increases from 12 to 28 months. The membranous bodies are composed of varying amounts of membranes, cytoplasm and empty vacuol...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-197603000-00003

    authors: Vaughan DW

    更新日期:1976-03-01 00:00:00

  • Morphogenesis of Lewy bodies: dissimilar incorporation of alpha-synuclein, ubiquitin, and p62.

    abstract::The formation of Lewy bodies (LBs) and their relationship to other types of nigral inclusions associated with Parkinson disease (PD), such as pale bodies (PBs), remain poorly understood. Known constituents of LBs include alpha-synuclein (alphaS) and ubiquitin (Ub), providing windows to their morphogenesis. Additionall...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/62.12.1241

    authors: Kuusisto E,Parkkinen L,Alafuzoff I

    更新日期:2003-12-01 00:00:00

  • The hyperacute form of allergic encephalomyelitis produced in rats without the aid of pertussis vaccine.

    abstract::The hyperacute form of experimental allergic encephalomyelitis (EAE), characterized by a short incubation period, severe paralysis, high mortality, and abundant polymorphonuclear leukocytes and fibrin in the lesions, was produced in rats without the use of pertussis vaccine (previously considered an essential requirem...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198905000-00003

    authors: Levine S,Saltzman A

    更新日期:1989-05-01 00:00:00

  • Hypoxia-inducible factor 1α mediates neuroprotection of hypoxic postconditioning against global cerebral ischemia.

    abstract::Hypoxia administered after transient global cerebral ischemia (tGCI) has been shown to induce neuroprotection in adult rats, but the underlying mechanisms for this protection are unclear. Here, we tested the hypothesis that hypoxic postconditioning (HPC) induces neuroprotection through upregulation of hypoxia-inducibl...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0000000000000118

    authors: Zhu T,Zhan L,Liang D,Hu J,Lu Z,Zhu X,Sun W,Liu L,Xu E

    更新日期:2014-10-01 00:00:00

  • LR11/SorLA expression is reduced in sporadic Alzheimer disease but not in familial Alzheimer disease.

    abstract::LR11 is an ApoE receptor that is enriched in the brain. We have shown that LR11 is markedly downregulated in patients with sporadic Alzheimer disease (AD). This finding led us to explore whether reduced LR11 expression reflects a primary mechanism of disease or merely a secondary consequence of other AD-associated cha...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/01.jnen.0000228205.19915.20

    authors: Dodson SE,Gearing M,Lippa CF,Montine TJ,Levey AI,Lah JJ

    更新日期:2006-09-01 00:00:00

  • Inhibition of neuroinflammation prevents injury to the serotonergic network after hypoxia-ischemia in the immature rat brain.

    abstract::The phenotypic identities and characterization of neural networks disrupted after neonatal hypoxia-ischemia (HI) in the preterm brain remain to be elucidated. Interruption of the central serotonergic (5-hydroxytryptamine [5-HT]) system can lead to numerous functional deficits, many of which match those in human preter...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3182020b7b

    authors: Wixey JA,Reinebrant HE,Buller KM

    更新日期:2011-01-01 00:00:00

  • Peri-Infarct Upregulation of the Oxytocin Receptor in Vascular Dementia.

    abstract::Vascular dementia (VaD) is cognitive decline linked to reduced cerebral blood perfusion, yet there are few therapeutic options to protect cognitive function following cerebrovascular accidents. The purpose of this study was to profile gene expression changes unique to VaD to identify and characterize disease relevant ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nlz023

    authors: McKay EC,Beck JS,Khoo SK,Dykema KJ,Cottingham SL,Winn ME,Paulson HL,Lieberman AP,Counts SE

    更新日期:2019-05-01 00:00:00