LRRK2 expression in normal and pathologic human brain and in human cell lines.

Abstract:

:Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been recently identified in families with autosomal-dominant late-onset Parkinson disease. We report that by reverse transcriptase-polymerase chain reaction, the mRNA of LRRK2 is expressed in soluble extracts of human brain, liver, and heart and in cultured human astrocytes, microglia, and oligodendroglia as well as in human neuroblastoma cell lines. We find by Western blotting using a polyclonal antibody of the leucine-rich repeat kinase 2 protein (Lrrk2) specific for C-terminal residues 2,511-2,527 that an apparent full-length protein and several of its fractions are expressed in soluble extracts of normal human brain. By immunocytochemistry, the antibody recognizes neurons, and more weakly astrocytes and microglia, in normal brain tissue. It intensely labels Lewy bodies in Parkinson disease and related neurodegenerative disorders. It also labels a subset of neurofibrillary tangles in Alzheimer disease and the Parkinsonism dementia complex of Guam (PDCG). It labels thorn-shaped astrocytes and oligodendroglial coiled bodies in PDCG; oligodendroglial inclusions in multiple system atrophy; Pick bodies in Pick disease; nuclear and cytoplasmic inclusions in Huntington disease; and intraneuronal and glial inclusions in amyotrophic lateral sclerosis. In summary, LRRK2 is constitutively expressed in neurons and also in glial cells of human brain. It strongly associates with pathological inclusions in several neurodegenerative disorders.

authors

Miklossy J,Arai T,Guo JP,Klegeris A,Yu S,McGeer EG,McGeer PL

doi

10.1097/01.jnen.0000235121.98052.54

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

953-63

issue

10

eissn

0022-3069

issn

1554-6578

pii

00005072-200610000-00003

journal_volume

65

pub_type

杂志文章
  • Kinin B1 receptor expression and function on human brain endothelial cells.

    abstract::The kinin B1 receptor is an inducible receptor expressed in response to inflammatory mediators. We sought to determine whether kinin B1 receptor can be expressed on human brain endothelial cells (HBECs) in vitro and whether signaling via this receptor can regulate permeability and chemokine production properties of th...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/59.10.896

    authors: Prat A,Biernacki K,Pouly S,Nalbantoglu J,Couture R,Antel JP

    更新日期:2000-10-01 00:00:00

  • The acyl-coenzyme A: cholesterol acyltransferase inhibitor CI-1011 reverses diffuse brain amyloid pathology in aged amyloid precursor protein transgenic mice.

    abstract::Cerebral accumulation of amyloid-beta (Abeta) is characteristic of Alzheimer disease and of amyloid precursor protein (APP) transgenic mice. Here, we assessed the efficacy of CI-1011, an inhibitor of acyl-coenzyme A:cholesterol acyltransferase, which is suitable for clinical use, in reducing amyloid pathology in both ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3181e77ed9

    authors: Huttunen HJ,Havas D,Peach C,Barren C,Duller S,Xia W,Frosch MP,Hutter-Paier B,Windisch M,Kovacs DM

    更新日期:2010-08-01 00:00:00

  • Upregulation of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha in leptomeningeal vascular malformations of Sturge-Weber syndrome.

    abstract::Cutaneous and leptomeningeal vascular malformations are hallmarks of the Sturge-Weber Syndrome (SWS), resulting in chronic ischemic tissue damage. The mechanisms underlying the pathobiology of these progressive lesions are unknown. Aberrant expression of angiogenic factors has been implicated in the genesis and mainte...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/nen.0b013e31802d9011

    authors: Comati A,Beck H,Halliday W,Snipes GJ,Plate KH,Acker T

    更新日期:2007-01-01 00:00:00

  • Morphological Alterations of the Sarcotubular System in Permanent Myopathy of Hereditary Hypokalemic Periodic Paralysis with a Mutation in the CACNA1S Gene.

    abstract::We investigated the immunohistochemical localization of several proteins related to excitation-contraction coupling and ultrastructural alterations of the sarcotubular system in biopsied muscles from a father and a daughter in a family with permanent myopathy with hypokalemic periodic paralysis (PMPP) due to a mutatio...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nlaa098

    authors: Nagasaka T,Hata T,Shindo K,Adachi Y,Takeuchi M,Saito K,Takiyama Y

    更新日期:2020-12-04 00:00:00

  • Somatostatin receptor type 2 undergoes plastic changes in the human epileptic dentate gyrus.

    abstract::Temporal lobe epilepsy (TLE) is characterized by hippocampal sclerosis together with profound losses and phenotypic changes of different classes of interneurons, including those expressing somatostatin (SRIF). To understand the functional significance of the plasticity of SRIF transmission in TLE, unraveling the statu...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/01.jnen.0000186923.50215.50

    authors: Csaba Z,Pirker S,Lelouvier B,Simon A,Videau C,Epelbaum J,Czech T,Baumgartner C,Sperk G,Dournaud P

    更新日期:2005-11-01 00:00:00

  • Abnormalities in neural progenitor cells in a dog model of lysosomal storage disease.

    abstract::Lysosomal storage disorders constitute a large group of genetic diseases, many of which are characterized by mental retardation and other neurologic symptoms. The mechanisms of neural dysfunction remain poorly understood. Because neural progenitor cells (NPCs) are fundamentally important to normal brain development an...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/nen.0b013e31812571c8

    authors: Walton RM,Wolfe JH

    更新日期:2007-08-01 00:00:00

  • Cerebellar ataxia in patients with mitochondrial DNA disease: a molecular clinicopathological study.

    abstract::Cerebellar ataxia is a prominent clinical symptom in patients with mitochondrial DNA (mtDNA) disease. This is often progressive with onset in young adulthood. We performed a detailed neuropathologic investigation of the olivary-cerebellum in 14 genetically and clinically well-defined patients with mtDNA disease. Quant...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e318244477d

    authors: Lax NZ,Hepplewhite PD,Reeve AK,Nesbitt V,McFarland R,Jaros E,Taylor RW,Turnbull DM

    更新日期:2012-02-01 00:00:00

  • Dysferlin, annexin A1, and mitsugumin 53 are upregulated in muscular dystrophy and localize to longitudinal tubules of the T-system with stretch.

    abstract::Mutations in dysferlin cause an inherited muscular dystrophy because of defective membrane repair. Three interacting partners of dysferlin are also implicated in membrane resealing: caveolin-3 (in limb girdle muscular dystrophy type 1C), annexin A1, and the newly identified protein mitsugumin 53 (MG53). Mitsugumin 53 ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e31821350b0

    authors: Waddell LB,Lemckert FA,Zheng XF,Tran J,Evesson FJ,Hawkes JM,Lek A,Street NE,Lin P,Clarke NF,Landstrom AP,Ackerman MJ,Weisleder N,Ma J,North KN,Cooper ST

    更新日期:2011-04-01 00:00:00

  • TAR DNA-binding protein 43 immunohistochemistry reveals extensive neuritic pathology in FTLD-U: a midwest-southwest consortium for FTLD study.

    abstract::TAR DNA-binding protein 43 (TDP-43) is a major component of the inclusions in frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U). We studied TDP-43 pathology in the hippocampus and frontal cortex of autopsy brains from patients with FTLD-U (n = 68), dementia lacking distinctive histopathology (n ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章,多中心研究

    doi:10.1097/NEN.0b013e31816a12a6

    authors: Hatanpaa KJ,Bigio EH,Cairns NJ,Womack KB,Weintraub S,Morris JC,Foong C,Xiao G,Hladik C,Mantanona TY,White CL 3rd

    更新日期:2008-04-01 00:00:00

  • Report of a Novel Case of Anaplastic Olfactory Groove Meningioma and Its Methylation Subtype.

    abstract::We report a novel case of a World Health Organization grade 3 anaplastic meningioma arising from the olfactory groove in an 83-year-old woman. Molecular and methylation profiling confirm this lesion to be an NF2 subtype, methylation class intermediate type B meningioma. As most meningiomas in this location are indolen...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nlx094

    authors: Foo ASC,Tan DTM,Tan CL,Sahm F,von Deimling A,Yeo TT

    更新日期:2017-12-01 00:00:00

  • Temporal and spatial expression of major myelin proteins in the human fetal spinal cord during the second trimester.

    abstract::Immunohistochemical identification of myelin basic protein (MBP) is a sensitive method for assessing myelination in the human fetal central nervous system (CNS). However, the temporospatial relationship of expression of two other major myelin proteins, proteolipid protein (PLP) and myelin-associated glycoprotein (MAG)...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199606000-00008

    authors: Weidenheim KM,Bodhireddy SR,Rashbaum WK,Lyman WD

    更新日期:1996-06-01 00:00:00

  • Altered Mitochondria, Protein Synthesis Machinery, and Purine Metabolism Are Molecular Contributors to the Pathogenesis of Creutzfeldt-Jakob Disease.

    abstract::Neuron loss, synaptic decline, and spongiform change are the hallmarks of sporadic Creutzfeldt-Jakob disease (sCJD), and may be related to deficiencies in mitochondria, energy metabolism, and protein synthesis. To investigate these relationships, we determined the expression levels of genes encoding subunits of the 5 ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nlw048

    authors: Ansoleaga B,Garcia-Esparcia P,Llorens F,Hernández-Ortega K,Carmona Tech M,Antonio Del Rio J,Zerr I,Ferrer I

    更新日期:2016-08-01 00:00:00

  • Reduced expression of the P2 form of the gap junction protein connexin43 in malignant meningiomas.

    abstract::Neoplastic transformation is often associated with aberrant gap junctional intercellular communication. We assessed mutations and expression of the connexin43 (Cx43) gene in 49 intracranial meningiomas. SSCP analyses followed by direct DNA sequencing showed GCG-->GTG (Ala-->Val) transition mutation in codon 253 of the...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:

    authors: Sato K,Gratas C,Lampe J,Biernat W,Kleihues P,Yamasaki H,Ohgaki H

    更新日期:1997-07-01 00:00:00

  • 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 ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nlx038

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

    更新日期:2017-07-01 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

  • Cerebrovascular smooth muscle actin is increased in nondemented subjects with frequent senile plaques at autopsy: implications for the pathogenesis of Alzheimer disease.

    abstract::We previously found that vascular smooth muscle actin (SMA) is reduced in the brains of patients with late stage Alzheimer disease (AD) compared with brains of nondemented, neuropathologically normal subjects. To assess the pathogenetic significance and disease specificity of this finding, we studied 3 additional pati...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e31819e6334

    authors: Hulette CM,Ervin JF,Edmonds Y,Antoine S,Stewart N,Szymanski MH,Hayden KM,Pieper CF,Burke JR,Welsh-Bohmer KA

    更新日期:2009-04-01 00:00:00

  • The mucopolysaccharides of the ground substance of the human brain.

    abstract::The concept of the presence of mucopolysaccharides forming an interstitial ground substance in central nervous tissues is revived. The biochemical reports of both neutral and acid mucopolysaccharides in both gray and white matter of the normal brain are reviewed. The earlier histochemical reports and the histochemical...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198001000-00001

    authors: Feigin I

    更新日期:1980-01-01 00:00:00

  • Primary rhabdomyosarcoma of the cerebellum--a light, electron microscopic, and immunohistochemical study.

    abstract::A primary cerebellar rhabdomyosarcoma (RMS) in a six and a half year old boy is reported. Microscopy of the surgical material revealed lobules of closely packed cells with a high mitotic rate, pleomorphic hyperchromatic nuclei and scant cytoplasm. At their periphery, the lobules merged with rounded cells with similar ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198407000-00008

    authors: Hinton DR,Halliday WC

    更新日期:1984-07-01 00:00:00

  • Nitric oxide synthase activity and expression in experimental diabetic neuropathy.

    abstract::The changes of nitric oxide synthase (NOS) activity and expression in experimental diabetic neuropathy have not been examined. Increases in ganglia NOS might be similar to those that follow axotomy, whereas declines in endothelial NOS (eNOS) and immunological NOS (iNOS) might explain dysfunction of microvessels or mac...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/59.9.798

    authors: Zochodne DW,Verge VM,Cheng C,Höke A,Jolley C,Thomsen K,Rubin I,Lauritzen M

    更新日期:2000-09-01 00:00:00

  • Cysteine-S-sulfate: brain damaging metabolite in sulfite oxidase deficiency.

    abstract::Cysteine-S-sulfate is an abnormal metabolite discovered in the urine and blood of a patient with cysteine oxidase deficiency, a rare disorder of sulfur amino acid metabolism associated with brain damage and mental retardation. The molecular structure of cysteine-S-sulfate closely resembles that of glutamate and relate...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-197503000-00005

    authors: Olney JW,Misra CH,de Gubareff T

    更新日期:1975-03-01 00:00:00

  • Traumatically induced reactive change as visualized through the use of monoclonal antibodies targeted to neurofilament subunits.

    abstract::Reactive axonal change has long been recognized as a feature of traumatic brain injury. To date, the histological methods used to identify reactive axons have been of limited utility, and they have not provided insight into the initial intraaxonal event that triggers reactive change. In this investigation, monoclonal ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199203000-00006

    authors: Yaghmai A,Povlishock J

    更新日期:1992-03-01 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

  • Expression of cell adhesion molecules in inflammatory myopathies and Duchenne dystrophy.

    abstract::Cell adhesion molecules participate in target-effector cell interactions in cell-mediated cytotoxicity and in leukodiapedesis in inflammatory diseases. Two ligand-receptor pairs may play a role in the adhesion of cytotoxic T cells to their targets: 1) intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199407000-00008

    authors: De Bleecker JL,Engel AG

    更新日期:1994-07-01 00:00:00

  • Retinal tumor induction by ocular inoculation of human adneovirus in 3-day-old rats.

    abstract::A direct causal relationship between a human DNA virus, adeno serotype 12, and malignant transformation in target cells (sensory retinal neuronal precursors) was suggested by the development of a remarkably uniform retinoblastoma-like neoplasm in rats. In order to focus upon incipient photoreceptor differentiation, 27...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-197501000-00003

    authors: Mukai N,Murao T

    更新日期:1975-01-01 00:00:00

  • Human cortex development: estimates of neuronal numbers indicate major loss late during gestation.

    abstract::This morphometric study explores temporal and topographic changes in the estimated neuronal number in human neocortex during the latter half of gestation and early infancy. Neuronal estimates are calculated from standardized measurements of cortical layer thickness and neuronal density in 6 neocortical regions in 9 hu...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:

    authors: Rabinowicz T,de Courten-Myers GM,Petetot JM,Xi G,de los Reyes E

    更新日期:1996-03-01 00:00:00

  • Three-dimensional analysis of the relationship between synaptic pathology and neuropil threads in Alzheimer disease.

    abstract::Recent studies have shown that the Alzheimer disease (AD) neocortex is characterized by a loss of large neurons, the presence of dilated terminal axons, widespread loss of synapses, and a disruption of the dendritic cytoskeleton which is manifested as Tau immunoreactive threads. In the present study we have investigat...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199207000-00003

    authors: Masliah E,Ellisman M,Carragher B,Mallory M,Young S,Hansen L,DeTeresa R,Terry RD

    更新日期:1992-07-01 00:00:00

  • 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 sig...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/63.12.1236

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

    更新日期:2004-12-01 00:00:00

  • Neuropathological features of frontotemporal dementia and parkinsonism linked to chromosome 17q21-22 (FTDP-17): Duke Family 1684.

    abstract::Frontotemporal dementia with parkinsonism (FTDP-17) is an autosomal dominant disorder that presents clinically with dementia, extrapyramidal signs, and behavioral disturbances in mid-life and progresses to death within 5 to 10 years. Pathologically, the disorder is characterized by variable neuronal loss and gliosis i...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199908000-00008

    authors: Hulette CM,Pericak-Vance MA,Roses AD,Schmechel DE,Yamaoka LH,Gaskell PC,Welsh-Bohmer KA,Crowther RA,Spillantini MG

    更新日期:1999-08-01 00:00:00

  • The effects of additional pathology on the cognitive deficit in Alzheimer disease.

    abstract::The diagnosis of Alzheimer disease (AD) according to current criteria is a combined clinical and pathological exercise. The clinical discrimination of AD from other types of dementia may be complicated when the patient suffers from more than one disease. In particular the concomitant presence of other neurological con...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199702000-00007

    authors: Nagy Z,Esiri MM,Jobst KA,Morris JH,King EM,McDonald B,Joachim C,Litchfield S,Barnetson L,Smith AD

    更新日期:1997-02-01 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