Abnormal alpha-synuclein interactions with Rab proteins in alpha-synuclein A30P transgenic mice.

Abstract:

:Mutation A30P in the alpha-synuclein gene is a cause of familial Parkinson disease. Transgenic mice expressing wild mouse and mutant human A30P alpha-synuclein, Tg5093 mice (Tg), show a progressive motor disorder characterized by tremor, rigidity, and dystonia, accompanied by accumulation of alpha-synuclein in the soma and neurites and by a conspicuous gliosis beginning in the hippocampal formation at the age of 7 to 8 months and spreading throughout the CNS. Impaired short-term changes in synaptic strength have also been documented in hippocampal slices from Tg mice. Alpha-synuclein aggregates of approximately 34 and 70 kDa, in addition to the band of 17 kDa, corresponding to the molecular weight of alpha-synuclein, were recovered in the PBS-soluble fraction of brain homogenates from Tg mice but not from brain samples from age-matched wildtype littermates. MPTP-treated Tg and wildtype mice produced alpha-synuclein aggregates in the PBS-, deoxycholate-, and SDS-soluble fractions. Aggregates of alpha-synuclein, although with different molecular weights, were also observed in rotenone-treated Tg and wildtype mice. Pull-down studies with members of the Rab protein family have shown that alpha-synuclein from Tg mice interacts with Rab3a, Rab5, and Rab8. This binding is not due to the amount of alpha-synuclein (levels of which are higher in Tg mice) and it is not dependent on the amount of Rab protein used in the assay. Rather, alpha-synuclein interactions with Rab proteins are due to mutant alpha-synuclein as demonstrated in Rab pull-down assays with recombinant of wildtype and mutant A30P human alpha-synuclein. Since Rab3a, Rab5, and Rab8 are important proteins involved in synaptic vesicle trafficking and exocytosis at the synapse, vesicle endocytosis, and trans-Golgi transport, respectively, it can be suggested that these functions are impaired in Tg mice. This rationale is consistent with previous data showing that short-term hippocampal synaptic plasticity is altered and that alpha-synuclein accumulates in the cytoplasm of neurons in Tg mice.

authors

Dalfó E,Gómez-Isla T,Rosa JL,Nieto Bodelón M,Cuadrado Tejedor M,Barrachina M,Ambrosio S,Ferrer I

doi

10.1093/jnen/63.4.302

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

302-13

issue

4

eissn

0022-3069

issn

1554-6578

journal_volume

63

pub_type

杂志文章
  • Porphyrin-laser photodynamic induction of focal brain necrosis.

    abstract::A noninvasive photodynamic method has been developed to produce focal brain necrosis using porphyrin activated in vivo with laser light. After peripheral injection of the photosensitive porphyrin derivative, Photofrin I, mice were irradiated on the posterior lateral aspect of the head through the intact depilated scal...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198909000-00005

    authors: Stroop WG,Battles EJ,Townsend JJ,Schaefer DC,Baringer JR,Straight RC

    更新日期:1989-09-01 00:00:00

  • Immunocytochemical double labeling of glial fibrillary acidic protein and transferrin permits the identification of astrocytes and oligodendrocytes in the rat brain.

    abstract::Sequential immunocytochemical double labeling of glial fibrillary acidic protein (GFAP) and transferrin (Tf) was used for the simultaneous identification of astrocytes and oligodendrocytes in paraffin-embedded sections of the rat brain. Paraformaldehyde or formalin-alcohol-acetic acid fixation followed by protease tre...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199103000-00007

    authors: Martin SM,Landel HB,Lansing AJ,Vijayan VK

    更新日期:1991-03-01 00:00:00

  • The side population of gliomas exhibits decreased cell migration.

    abstract::Side population (SP) cells identified using the Hoechst 33342 fluorescent dye efflux technique overlap with the tumor stem cell fraction that is responsible for tumorigenesis and recurrence in malignant gliomas. Because diffuse invasion of glioma cells represents the main obstacle to successful therapy and underlies r...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3181e04739

    authors: Weber K,Paulus W,Senner V

    更新日期:2010-06-01 00:00:00

  • Electron microscopic study of capillary wall in human cerebral edema.

    abstract::Cortical biopsies of 17 patients with diagnoses of congenital malformation, cerebral tumor or brain trauma complicated by subdural hematoma or hygroma were studied with the electron microscope; the alterations of the blood-brain barrier in moderate and severe perifocal cerebral edema were observed. Moderate edema was ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-198005000-00006

    authors: Castejón OJ

    更新日期:1980-05-01 00:00:00

  • Alpha-synuclein lesions in normal aging, Parkinson disease, and Alzheimer disease: evidence from the Baltimore Longitudinal Study of Aging (BLSA).

    abstract::Alpha-synuclein (alpha-synuclein) lesions are characteristic of idiopathic Parkinson disease (PD) and other alpha-synucleinopathies. To study the frequency of alpha-synuclein lesions in normal aging and how frequently they coexist with lesions of Alzheimer disease (AD), we examined the autopsy brains from normal and d...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/64.2.156

    authors: Mikolaenko I,Pletnikova O,Kawas CH,O'Brien R,Resnick SM,Crain B,Troncoso JC

    更新日期:2005-02-01 00:00:00

  • Bcl-2 immunoreactive cells with immature neuronal phenotype exist in the nonepileptic adult human brain.

    abstract::Bcl-2, a cell death suppressor protein, is expressed during brain development but is largely down-regulated in the adult central nervous system. We previously reported strong expression of bcl-2 in small, "oligodendrocyte-like" cells (OLC) found in glioneuronal hamartias. These hamartias are microscopic cell rests fou...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/59.2.113

    authors: Yachnis AT,Roper SN,Love A,Fancey JT,Muir D

    更新日期:2000-02-01 00:00:00

  • Temporal lobe epilepsy associated up-regulation of metabotropic glutamate receptors: correlated changes in mGluR1 mRNA and protein expression in experimental animals and human patients.

    abstract::Aberrant axonal reorganization and altered distribution of neurotransmitter receptor subtypes have been proposed as major pathogenic mechanisms for hippocampal hyperexcitability in chronic temporal lobe epilepsies (TLE). Recent data point to excitatory class I metabotropic glutamate receptors (mGluR1 and mGluR5) as in...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/59.1.1

    authors: Blümcke I,Becker AJ,Klein C,Scheiwe C,Lie AA,Beck H,Waha A,Friedl MG,Kuhn R,Emson P,Elger C,Wiestler OD

    更新日期:2000-01-01 00:00:00

  • An ultrastructural study of subacute combined degeneration of the spinal cord in vitamin B12-deficient rhesus monkeys.

    abstract::Prolonged deprivation of vitamin B12 in rhesus monkeys produced changes in the central nervous system that were indistinguishable topographically and histologically from those of human subacute combined degeneration. Ultrastructural studies of early lesions of the spinal cord disclosed a degeneration of myelin charact...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-197805000-00006

    authors: Agamanolis DP,Victor M,Harris JW,Hines JD,Chester EM,Kark JA

    更新日期:1978-05-01 00:00:00

  • Macrophage properties during peripheral nervous tissue rejection in vitro.

    abstract::The present study introduces an in vitro model of xenogeneic peripheral nerve rejection to analyze the role of macrophages in this complex immunological situation. Nerve-sensitized mouse peritoneal exudate cells were co-cultured with rat peripheral nerve segments. The cultured rat nerve segments were fulminantly rejec...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199401000-00007

    authors: Brück W,Brück Y,Maruschak B,Friede RL

    更新日期:1994-01-01 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

  • Inducible nitric oxide synthase (iNOS) and nitrotyrosine immunoreactivity in the spinal cords of transgenic mice with a G93A mutant SOD1 gene.

    abstract::We performed a prospective, longitudinal immunohistochemical study of the spinal cords of transgenic mice with a G93A mutant SOD1 gene at 4 fixed points in time, using antibodies to inducible nitric oxide synthase (iNOS) and nitrotyrosine. The purpose of this study was to characterize the temporal and topographic dist...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/60.9.839

    authors: Sasaki S,Warita H,Abe K,Iwata M

    更新日期:2001-09-01 00:00:00

  • Sudden infant death syndrome: postnatal changes in the volumes of the pons, medulla and cervical spinal cord.

    abstract::The brainstem and cervical spinal cord were sampled from 45 cases of sudden infant death syndrome (SIDS), from 17 control cases without neurological disease, and from three negative control cases with abnormal growth of the central nervous system (36-98 postconceptional weeks). Morphometric analyses were performed on ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:

    authors: O'Kusky JR,Kozuki DE,Norman MG

    更新日期:1995-07-01 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

  • 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

  • Characteristics of an explosive blast-induced brain injury in an experimental model.

    abstract::Mild traumatic brain injury resulting from exposure to an explosive blast is associated with significant neurobehavioral outcomes in soldiers. Little is known about the neuropathologic consequences of such an insult to the human brain. This study is an attempt to understand the effects of an explosive blast in a large...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e318235bef2

    authors: de Lanerolle NC,Bandak F,Kang D,Li AY,Du F,Swauger P,Parks S,Ling G,Kim JH

    更新日期:2011-11-01 00:00:00

  • Hippocampal neurons predisposed to neurofibrillary tangle formation are enriched in type II calcium/calmodulin-dependent protein kinase.

    abstract::The microtubule-associated phosphoprotein, tau, is an integral component of paired helical filaments in Alzheimer neurofibrillary tangles (NFT). The mechanism of NFT formation is unknown but aberrant phosphorylation of tau may be contributory. Calcium/calmodulin-dependent protein kinase type II (CaM kinase II), the mo...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199001000-00006

    authors: McKee AC,Kosik KS,Kennedy MB,Kowall NW

    更新日期:1990-01-01 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

  • Dysembryoplastic neuroeptihelial tumor (DNT): an immunohistochemical and ultrastructural study.

    abstract::To assess the range of differentiation of the cells comprising dysembryoplastic neuroepithelial tumor (DNT), particularly the oligodendrocyte-like cells (OLC), 14 DNT were immunochemically studied with a spectrum of neuronal and glial markers. Eight tumors were also studied ultrastructurally. Neurofilament protein, cl...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199403000-00010

    authors: Hirose T,Scheithauer BW,Lopes MB,VandenBerg SR

    更新日期:1994-03-01 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

  • Neuroanatomic connectivity of the human ascending arousal system critical to consciousness and its disorders.

    abstract::The ascending reticular activating system (ARAS) mediates arousal, an essential component of human consciousness. Lesions of the ARAS cause coma, the most severe disorder of consciousness. Because of current methodological limitations, including of postmortem tissue analysis, the neuroanatomic connectivity of the huma...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3182588293

    authors: Edlow BL,Takahashi E,Wu O,Benner T,Dai G,Bu L,Grant PE,Greer DM,Greenberg SM,Kinney HC,Folkerth RD

    更新日期:2012-06-01 00:00:00

  • Blockade of interleukin 6 signaling improves the survival rate of transplanted bone marrow stromal cells and increases locomotor function in mice with spinal cord injury.

    abstract::Bone marrow stromal cells (BMSCs) have the potential to improve functional recovery in patients with spinal cord injury (SCI); however, they are limited by low survival rates after transplantation in the injured tissue. Our objective was to clarify the effects of a temporal blockade of interleukin 6 (IL-6)/IL-6 recept...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3182a79de9

    authors: Tan Y,Uchida K,Nakajima H,Guerrero AR,Watanabe S,Hirai T,Takeura N,Liu SY,Johnson WE,Baba H

    更新日期:2013-10-01 00:00:00

  • Neurodegeneration in mice resulting from loss of functional selenoprotein P or its receptor apolipoprotein E receptor 2.

    abstract::Selenoprotein P (Sepp1) is involved in selenium homeostasis. Mice with a deletion of Sepp1, replacement of it by the shortened form Sepp1(Delta240-361), or deletion of its receptor apolipoprotein E receptor 2 develop severe neurologic dysfunction when fed low-selenium diet. Because the brainstems of Sepp1(-/-) mice ha...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e318160f347

    authors: Valentine WM,Abel TW,Hill KE,Austin LM,Burk RF

    更新日期:2008-01-01 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

  • Shrinkage of motor axons following systemic exposure to inorganic mercury.

    abstract::Systemically-administered inorganic mercury localizes to motor neurons, but it is not known if mercury injures these neurons. We therefore looked for signs of damage to the motor and sensory neurons of mice that had been exposed to inorganic mercury. Young adult mice were injected intraperitoneally with either 1 or 2 ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/00005072-199804000-00009

    authors: Pamphlett R,Png FY

    更新日期:1998-04-01 00:00:00

  • Loss of parvalbumin-positive neurons from the globus pallidus in animal models of Parkinson disease.

    abstract::The external segment of the globus pallidus (GPe) in humans and the equivalent structure in rodents, the globus pallidus (GP), influence signal processing in the basal ganglia under normal and pathological conditions. Parvalbumin (PV) immunoreactivity defines 2 main neuronal subpopulations in the GP/GPe: PV-immunoposi...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e3182717cba

    authors: Fernández-Suárez D,Celorrio M,Lanciego JL,Franco R,Aymerich MS

    更新日期:2012-11-01 00:00:00

  • Chemically induced rat Schwann cell neoplasia as a model for early-stage human peripheral nerve sheath tumors: phenotypic characteristics and dysregulated gene expression.

    abstract::Most malignant human tumors display a high degree of intratumoral heterogeneity at the time of diagnosis that contributes to treatment failure. This also applies to malignant peripheral nerve sheath tumors (MPNSTs) and aggressive soft tissue sarcomas that arise sporadically or in the context of neurofibromatosis type ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1097/NEN.0b013e31828ea4ac

    authors: Koelsch B,van den Berg L,Grabellus F,Fischer C,Kutritz A,Kindler-Röhrborn A

    更新日期:2013-05-01 00:00:00

  • Structural and Functional Abnormalities of the Neuromuscular Junction in the Trembler-J Homozygote Mouse Model of Congenital Hypomyelinating Neuropathy.

    abstract::Mutations in peripheral myelin protein 22 (PMP22) result in the most common form of Charcot-Marie-Tooth (CMT) disease, CMT1A. This hereditary peripheral neuropathy is characterized by dysmyelination of peripheral nerves, reduced nerve conduction velocity, and muscle weakness. APMP22 point mutation in L16P (leucine 16 ...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nlw004

    authors: Scurry AN,Heredia DJ,Feng CY,Gephart GB,Hennig GW,Gould TW

    更新日期:2016-04-01 00:00:00

  • Myeloperoxidase Associates With Degenerative Remodeling and Rupture of the Saccular Intracranial Aneurysm Wall.

    abstract::Rupture of a saccular intracranial aneurysm (sIA) is often fatal. Thus, early detection of rupture-prone sIAs is vital. Myeloperoxidase (MPO), derived mainly from neutrophils, associates with sIA rupture, and therefore its role in sIA pathogenesis warrants further studies. We analyzed MPO and its association with othe...

    journal_title:Journal of neuropathology and experimental neurology

    pub_type: 杂志文章

    doi:10.1093/jnen/nly028

    authors: Ollikainen E,Tulamo R,Lehti S,Hernesniemi J,Niemelä M,Kovanen PT,Frösen J

    更新日期:2018-06-01 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

  • 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