Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation.

Abstract:

:In the central nervous system, tuberous sclerosis complex (TSC) is characterized by a range of lesions including cortical tubers, white matter heterotopias, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs). Recent studies have implicated an important role for the TSC genes TSC1 and TSC2, in a signaling pathway involving the mammalian target of rapamycin (mTOR) kinase. We performed immunohistochemical and genetic analyses on SEGAs from 7 TSC patients, 4 with mutations in TSC1, and 3 with mutations in TSC2. SEGA cells show high levels of phospho-S6K, phospho-S6, and phospho-Stat3, all proteins downstream of and indicative of mTOR activation. Such expression is not seen in histologically normal control tissue. Five of 6 SEGAs also showed evidence of biallelic mutation of TSC1 or TSC2, suggesting that SEGAs develop due to complete loss of a functional tuberin-hamartin complex. We conclude that TSC SEGAs likely arise through a two-hit mechanism of biallelic inactivation of TSC1 or TSC2, leading to activation of the mTOR kinase.

authors

Chan JA,Zhang H,Roberts PS,Jozwiak S,Wieslawa G,Lewin-Kowalik J,Kotulska K,Kwiatkowski DJ

doi

10.1093/jnen/63.12.1236

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

1236-42

issue

12

eissn

0022-3069

issn

1554-6578

journal_volume

63

pub_type

杂志文章
  • The endoneurial content of lead related to the onset and severity of segmental demyelination.

    abstract::The endoneurial lead and water content was serially evaluated in the nerves of rats fed lead carbonate and related to the onset and severity of segmental demyelination and remyelination. Lead began to accumulate significantly in the endoneurium by 5 days, reached a maximum level (71 microgram/g dry weight) by 34 days,...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198011000-00008

    authors: Windebank AJ,McCall JT,Hunder HG,Dyck PJ

    更新日期:1980-11-01 00:00:00

  • Interleukin 10 protects the brain microcirculation from spirochetal injury.

    abstract::Spirochetal infections are an important cause of neurological disease. In previous studies of the pathogenesis of spirochetal brain infection, mice inoculated with Borrelia turicatae, an agent of tick-borne relapsing fever in North America, developed mild meningitis and parenchymal activation/infiltration by interleuk...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e318187a279

    authors: Londoño D,Carvajal J,Arguelles-Grande C,Marques A,Cadavid D

    更新日期:2008-10-01 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

  • Characterization of ubiquitinated intraneuronal inclusions in a novel Belgian frontotemporal lobar degeneration family.

    abstract::The most common histologic feature in patients with frontotemporal lobar degeneration (FTLD) is intracellular brain inclusions of yet uncharacterized proteins that react with antiubiquitin (Ub) antibodies, but not with tau or synuclein (FTLD-U). We identified a four-generation Belgian FTLD family in which 8 patients h...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/01.jnen.0000205147.39210.c7

    authors: Pirici D,Vandenberghe R,Rademakers R,Dermaut B,Cruts M,Vennekens K,Cuijt I,Lübke U,Ceuterick C,Martin JJ,Van Broeckhoven C,Kumar-Singh S

    更新日期:2006-03-01 00:00:00

  • Oxidative damage is the earliest event in Alzheimer disease.

    abstract::Recently, we demonstrated a significant increase of an oxidized nucleoside derived from RNA, 8-hydroxyguanosine (8OHG), and an oxidized amino acid, nitrotyrosine in vulnerable neurons of patients with Alzheimer disease (AD). To determine whether oxidative damage is an early- or end-stage event in the process of neurod...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/60.8.759

    authors: Nunomura A,Perry G,Aliev G,Hirai K,Takeda A,Balraj EK,Jones PK,Ghanbari H,Wataya T,Shimohama S,Chiba S,Atwood CS,Petersen RB,Smith MA

    更新日期:2001-08-01 00:00:00

  • In situ hybridization analysis for expression of myogenic regulatory factors in regenerating muscle of mdx mouse.

    abstract::Precise temporal and spatial coordination of expression of the myogenic regulatory factors (MRF) plays a critical role in the development of skeletal muscle. Whether this pattern is recapitulated postnatally during regeneration of mature muscle after injury is not known. The aim of this study was to determine the cell...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199605000-00002

    authors: Bhagavati S,Ghatpande A,Shafiq SA,Leung B

    更新日期:1996-05-01 00:00:00

  • Localized Hypertrophic Neuropathy as a Neoplastic Manifestation of KRAS-Mediated RASopathy.

    abstract::Localized hypertrophic neuropathy is a rare Schwann cell proliferation that usually affects single nerves from the extremities, and it is of unclear etiology in its pure form. RASopathies are a defined group of genetic diseases with overlapping clinical features, usually secondary to germline mutations in genes encodi...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nlaa034

    authors: Vizcaino MA,Belzberg A,Ahlawat S,Belakhoua S,Chen L,Staedtke V,Rodriguez FJ

    更新日期:2020-06-01 00:00:00

  • Loss of Perineuronal Net in ME7 Prion Disease.

    abstract::Microglial activation and behavioral abnormalities occur before neuronal loss in experimental murine prion disease; the behavioral changes coincide with a reduction in synaptic plasticity. Because synaptic plasticity depends on an intact perineuronal net (PN), a specialized extracellular matrix that surrounds parvalbu...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3181654386

    authors: Franklin SL,Love S,Greene JR,Betmouni S

    更新日期:2008-03-01 00:00:00

  • Apolipoprotein E alters metabolism of AbetaPP in cells engaged in beta-amyloidosis.

    abstract::Canine smooth muscle cells (SMCs), cultured from amyloid-affected brain blood vessels accumulate Alzheimer amyloid-beta peptide (Abeta) intracellularly, either spontaneously or after treatment with apolipoprotein E (apoE). ApoE is codeposited with Abeta, which suggests that apoE participates in Abeta accumulation. We ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199903000-00008

    authors: Mazur-Kolecka B,Frackowiak J,Krzeslowska J,Ramakrishna N,Haske T,Emmerling MR,Zhang W,Kim KS,Wisniewski HM

    更新日期:1999-03-01 00:00:00

  • Involvement of transverse tubules in induced myotonia.

    abstract::A single oral dose of clofibrate (30 mg/100 gm body weight) given to 250-300 gm male rats produced myotonic discharges from both the gastrocnemius and soleus muscles 2 hours after feeding. Rats fed the same dosage for 14 consecutive days exhibited electromyographic discharges consistent with profound myotonia. Fibers ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-197911000-00004

    authors: Ontell M,Paul HS,Adibi SA,Martin JL

    更新日期:1979-11-01 00:00:00

  • Nuclear factor-kappaB activation in axons and Schwann cells in experimental sciatic nerve injury and its role in modulating axon regeneration: studies with etanercept.

    abstract::Early inflammatory events may inhibit functional recovery after injury in both the peripheral and central nervous systems. We investigated the role of the inflammatory tumor necrosis factor/nuclear factor-kappaB (NF-kappaB) axis on events subsequent to sciatic nerve crush injury in adult rats. Electrophoretic mobility...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3181a7c14e

    authors: Smith D,Tweed C,Fernyhough P,Glazner GW

    更新日期:2009-06-01 00:00:00

  • Neuropathologic effects of intrathecal water.

    abstract::In attempting to control the pain of disseminated carcinoma, a variety of agents has been injected intrathecally. This report deals with the neuropathologic changes in spinal roots and spinal cord of four patients into whose lumbar sacs 100 to 285 ml of distilled water was infused. Survival following the procedure ra...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-197509000-00002

    authors: Kelly JM,Asbury AK,King JS

    更新日期:1975-09-01 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

  • Accumulation of aspartic acid421- and glutamic acid391-cleaved tau in neurofibrillary tangles correlates with progression in Alzheimer disease.

    abstract::Truncations of tau protein at aspartic acid421 (D421) and glutamic acid391 (E391) residues are associated with neurofibrillary tangles (NFTs) in the brains of Alzheimer disease (AD) patients. Using immunohistochemistry with antibodies to D421- and E391-truncated tau (Tau-C3 and MN423, respectively), we correlated the ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e31817275c7

    authors: Basurto-Islas G,Luna-Muñoz J,Guillozet-Bongaarts AL,Binder LI,Mena R,García-Sierra F

    更新日期:2008-05-01 00:00:00

  • Proliferative potential of sporadic and neurofibromatosis 2-associated schwannomas as studied by MIB-1 (Ki-67) and PCNA labeling.

    abstract::Neurofibromatosis 2 (NF2), a dominantly inherited disorder, is typically manifested as bilateral vestibular Schwannomas and predisposes to other nervous system tumors. Vestibular Schwannomas also occur sporadically but the onset is usually at an older age. Surgical and histological studies have shown that vestibular S...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199511000-00004

    authors: Antinheimo J,Haapasalo H,Seppälä M,Sainio M,Carpen O,Jääskeläinen J

    更新日期:1995-11-01 00:00:00

  • A Quantitative Analysis of Brain Soluble Tau and the Tau Secretion Factor.

    abstract::Neurofibrillary tangles (NFTs) represent products of insoluble tau protein in the brains of patients with Alzheimer disease (AD). The cerebrospinal fluid (CSF) tau level is a biomarker in AD diagnosis. The soluble portion of tau protein in brain parenchyma is presumably the source for CSF tau but this has not previous...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nlw105

    authors: Han P,Serrano G,Beach TG,Caselli RJ,Yin J,Zhuang N,Shi J

    更新日期:2017-01-01 00:00:00

  • Microglial activation parallels system degeneration in multiple system atrophy.

    abstract::Multiple system atrophy (MSA) is a neurodegenerative disorder that predominantly affects motor-related neuroanatomic structures. The role of microglia in MSA is unknown. To address this issue, we conducted quantitative image studies on the brains from 13 cases of MSA, comprising 8 cerebellar and 5 parkinsonian variant...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/63.1.43

    authors: Ishizawa K,Komori T,Sasaki S,Arai N,Mizutani T,Hirose T

    更新日期:2004-01-01 00:00:00

  • Subcellular localization of peptidylarginine deiminase 2 and citrullinated proteins in brains of scrapie-infected mice: nuclear localization of PAD2 and membrane fraction-enriched citrullinated proteins.

    abstract::Peptidylarginine deiminase (PAD) and citrullinated proteins have emerged as key molecules in various human diseases, but detailed subcellular localizations of PAD2 and citrullinated proteins are poorly mapped in brain under normal and pathologic conditions. We performed subcellular fractionation and electron microscop...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e318207559e

    authors: Jang B,Shin HY,Choi JK,Nguyen du PT,Jeong BH,Ishigami A,Maruyama N,Carp RI,Kim YS,Choi EK

    更新日期:2011-02-01 00:00:00

  • Astrocytic proteins in the dorsal and ventral roots in amyotrophic lateral sclerosis and Werdnig-Hoffmann disease.

    abstract::Abnormalities were detected by two-dimensional gel electrophoresis in the protein composition of both the dorsal and ventral roots of three of six patients who succumbed to amyotrophic lateral sclerosis (ALS). The abnormalities consisted of a cascade of acidic protein spots on silver-stained gels which were shown by i...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198411000-00005

    authors: Brock TO,McIlwain DL

    更新日期:1984-11-01 00:00:00

  • Pathological Relationship Between Adamantinomatous Craniopharyngioma and Adjacent Structures Based on QST Classification.

    abstract::The aim of this study was to clarify pathological and anatomical relationships between adamantinomatous craniopharyngiomas (ACP) and their surrounding structures. We previously established a QST classification scheme based on the apparent anatomic origin of the tumors. According to this classification, 13 type Q tumor...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nly083

    authors: Liu Y,Qi ST,Wang CH,Pan J,Fan J,Peng JX,Zhang X,Bao Y,Liu YW

    更新日期:2018-11-01 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

  • The CTSC-RAB38 Fusion Transcript Is Associated With the Risk of Hemorrhage in Brain Arteriovenous Malformations.

    abstract::Brain arteriovenous malformations (bAVMs) are congenital anomalies of blood vessels that cause intracranial hemorrhage in children and young adults. Chromosomal rearrangements and fusion genes play an important role in tumor pathogenesis, though the role of fusion genes in bAVM pathophysiological processes is unclear....

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nlaa126

    authors: Yan Z,Fan G,Li H,Jiao Y,Fu W,Weng J,Huo R,Wang J,Xu H,Wang S,Cao Y,Zhao J

    更新日期:2021-01-01 00:00:00

  • Endoplasmic reticulum stress in PLP-overexpressing transgenic rats: gray matter oligodendrocytes are more vulnerable than white matter oligodendrocytes.

    abstract::Studies dealing with transport of proteins from the oligodendrocyte cell body to the myelin sheath reveal the presence of different transport pathways. Proteolipid protein (PLP) is synthesized at the rough endoplasmic reticulum (ER) and then processed through the Golgi apparatus and transported to the myelin membranes...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/61.1.12

    authors: Bauer J,Bradl M,Klein M,Leisser M,Deckwerth TL,Wekerle H,Lassmann H

    更新日期:2002-01-01 00:00:00

  • Comparison of two quantitative methods for the evaluation of neuronal number in the frontal cortex in Alzheimer disease.

    abstract::How to assess the substantial neuronal loss in a neurodegenerative disease such as Alzheimer disease is still being debated. Recently, stereological procedures have been proposed that claim improved accuracy and statistical power, but the results of some of these investigations have been controversial. In this study w...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199711000-00004

    authors: Everall IP,DeTeresa R,Terry R,Masliah E

    更新日期:1997-11-01 00:00:00

  • Accumulation of prion protein in the peripheral nervous system in human prion diseases.

    abstract::After the finding that anti-prion antibodies stain sensory and sympathetic ganglia in variant Creutzfeldt-Jakob disease (vCJD), it was suggested that this localization supported the oral route of entry. However, prion accumulation subsequently also appeared in the peripheral nervous system (PNS) in sporadic cases. Thi...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/01.jnen.0000175330.66715.08

    authors: Lee CC,Kuo LT,Wang CH,Scaravilli F,An SF

    更新日期:2005-08-01 00:00:00

  • Immunity to transplantable nitrosourea-induced neurogenic tumors. II. Immunoprophylaxis of tumors of the brain.

    abstract::An effective method was sought to immunize rats against the growth of intracerebrally (IC) injected T9 tumor, a gliosarcoma cell line. Rats which were immunized with either 10(6) T9 cells mixed with 0.14 mg C. parvum, or 10(7) irradiated T9 cells showed tumor immunity to intradermal (ID) transplantation. However, to o...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198303000-00002

    authors: Kida Y,Cravioto H,Hochwald GM,Hochgeschwender U,Ransohoff J

    更新日期:1983-03-01 00:00:00

  • Expression of PROX1 Is a common feature of high-grade malignant astrocytic gliomas.

    abstract::PROX1 is a prospero-related transcription factor that plays a critical role in the development of various organs including the mammalian lymphatic and central nervous systems; it controls cell proliferation and differentiation through different transcription pathwaysand has both oncogenic and tumor-suppressive functio...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3181ca4767

    authors: Elsir T,Eriksson A,Orrego A,Lindström MS,Nistér M

    更新日期:2010-02-01 00:00:00

  • Staging of argyrophilic grains: an age-associated tauopathy.

    abstract::We have reported that the ambient gyrus is the site with the greatest accumulation of argyrophilic grains (AGs) and that the degeneration of the ambient gyrus is responsible for dementia with grains. Here we analyzed 1,405 serial autopsy cases from 2 hospitals and detected AGs only in cases older than 56 years of age....

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/63.9.911

    authors: Saito Y,Ruberu NN,Sawabe M,Arai T,Tanaka N,Kakuta Y,Yamanouchi H,Murayama S

    更新日期:2004-09-01 00:00:00

  • Accumulation of Alzheimer amyloid-beta peptide in cultured myocytes is enhanced by serum and reduced by cerebrospinal fluid.

    abstract::Smooth muscle cells cultured from leptomeningeal vessels from old dogs with amyloid-angiopathy accumulate intracellular deposits that are immunoreactive for amyloid-beta peptide (A beta). We used this cellular model in the present study to examine the influence of sera and cerebrospinal fluid on intracellular accumula...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199703000-00005

    authors: Mazur-Kolecka B,Frackowiak J,Carroll RT,Wisniewski HM

    更新日期:1997-03-01 00:00:00

  • Lumbar motoneurons of man: III. The number and diameter distribution of large- and intermediate- diameter cytons by nuclear columns.

    abstract::In a recent study we estimated the number and frequency distribution of the diameters of the cytons of all of the combined motoneuron columns of L3, L4 and L5 ventral horn of the spinal cord of man. In the present study we have estimated the number and frequency distribution of the diameter of motoneuron cytons in the...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-197711000-00007

    authors: Kawamura Y,Dyck PJ

    更新日期:1977-11-01 00:00:00