Abstract:
:G-protein coupled receptor kinases (GRKs) constitute a serine/threonine kinase family playing a major role in agonist-induced phosphorylation and desensitization of G-protein coupled receptors. Recently, GRK2 and GRK5 have been demonstrated to phosphorylate alpha-synuclein (Ser129) and other synuclein isoforms. We studied colocalization of GRK2, GRK5, alpha-synuclein, and tau in neurodegenerative disorders characterized by fibrillary tau inclusions and/or alpha-synuclein-enriched Lewy bodies. We found that Lewy bodies were negative for both GRK2 and GRK5 in Lewy body disease (LBD) and LBD mixed with Alzheimer disease (AD + LBD). Instead, GRK2 but not GRK5 colocalized with 40% to 50% of neurofibrillary tangles in AD + LBD and AD brains. In disorders with less prominent alpha-synucleinopathy, neuronal and glial fibrillary tau deposits known to contain distinct subsets of tau isoforms were also positive for GRK2. These deposits included tufted astrocytes and coiled bodies in progressive supranuclear palsy, astrocytic plaques in corticobasal degeneration, and Pick bodies in Pick disease. In addition, paired helical filaments isolated from AD and AD + LBD brains were found to immunogold-label for GRK2, suggesting that GRK2 could be a potential tau kinase associated with fibrillary tau. Our studies indicate that GRK2 is a novel component of neuronal and glial fibrillary tau deposits with no preference in tau isoform binding. GRK2 may play a role in hyperphosphorylation of tau in tauopathies.
journal_name
J Neuropathol Exp Neuroljournal_title
Journal of neuropathology and experimental neurologyauthors
Takahashi M,Uchikado H,Caprotti D,Weidenheim KM,Dickson DW,Ksiezak-Reding H,Pasinetti GMdoi
10.1097/01.jnen.0000248542.82681.12subject
Has Abstractpub_date
2006-12-01 00:00:00pages
1157-69issue
12eissn
0022-3069issn
1554-6578pii
00005072-200612000-00008journal_volume
65pub_type
杂志文章abstract::The aim of this study was to clarify the relationship between craniopharyngiomas (CP) and the third ventricle floor by analyzing the membranes between them. Eight fetal specimens were first examined by hematoxylin and eosin and immunofluorescence staining to determine optimal markers for identifying membrane structure...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlaa087
更新日期:2020-09-01 00:00:00
abstract::Axonal damage is the major cause of irreversible neurologic disability in patients with multiple sclerosis. Although axonal damage correlates with antibodies against neurofilament light (NF-L) protein, a major component of the axonal cytoskeleton, the possible pathogenic role of autoimmunity to axonal antigens such as...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/nen.0b013e318040ad5c
更新日期:2007-04-01 00:00:00
abstract::Tissue microarrays (TMAs), also known as "tissue chips," are a recently developed method that allows small cores or discs of tissue from dozens or hundreds of (usually paraffin-embedded) specimens to be re-embedded in a tissue block, which can then be further sectioned. The tissue cores can subsequently be studied usi...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章,评审
doi:10.1093/jnen/61.8.653
更新日期:2002-08-01 00:00:00
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
更新日期:1992-03-01 00:00:00
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
更新日期:1977-11-01 00:00:00
abstract::The choroid plexus (CP) is considered to be a point of leukocyte entry into the CNS during normal immune surveillance and in neuroinflammatory diseases. The structural and functional alterations within the CP that support this migration are not understood. We used quantitative, high-resolution, 3-dimensional (3-D) flu...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000127
更新日期:2014-11-01 00:00:00
abstract::An A and L system of neutral amino acid transport has been demonstrated previously in cerebral microvessels in vivo and in isolated microvessels in vitro. This report describes the neutral amino acid transport properties of cultured cerebral endothelial cells and investigates the influence of astroglia on the transpor...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198303000-00008
更新日期:1983-03-01 00:00:00
abstract::Borna disease virus (BDV) replicates only in cells in the central (CNS) and peripheral (PNS) nervous system in adult rats. Infection of the nervous system is associated with a transient, intense mononuclear meningoencephalitis and immunemediated loss of BDV-infected neurons. The identification of BDV antigen in neuron...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198911000-00005
更新日期:1989-11-01 00:00:00
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
更新日期:1997-11-01 00:00:00
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
更新日期:1992-07-01 00:00:00
abstract::Lhermitte-Duclos disease (LDD) is a rare cerebellar tumor associated with Cowden disease (CD) and germline mutations in the PTEN gene. To further define these relationships, we reviewed clinical and pathologic findings in 31 LDD cases and analyzed the status of the PTEN pathway in 11 of them. We hypothesized that the ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章,评审
doi:10.1093/jnen/64.4.341
更新日期:2005-04-01 00:00:00
abstract::Oligodendrogliomas are characterized by frequent loss of heterozygosity (LOH) on chromosomes 1p and 19q, but additional genetic alterations are likely to be involved. In this study, we screened 28 oligodendrogliomas (WHO grade II) and 20 anaplastic oligodendrogliomas (WHO grade III) for alterations in the RB1/CDK4/p16...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/60.12.1181
更新日期:2001-12-01 00:00:00
abstract::The development and differentiation of oligodendrocytes (OC) in developing mouse spinal cord (MSC) were investigated by correlative analysis of light and electron microscopy (EM), and immunoperoxidase studies for glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP). The sequential development of glial...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198609000-00003
更新日期:1986-09-01 00:00:00
abstract::This study describes, for the first time, the neuropathy of zinc pyridinethione (ZPT) toxicity in rats. Although hind-limb weakness has been previously reported as a consequence of dietary ZPT ingestion in rats and rabbits, the cause of the paralysis has been unexplained. Sequential morphologic studies in rats fed a d...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197909000-00007
更新日期:1979-09-01 00:00:00
abstract::Lewy body-like hyaline inclusions in the soma and swollen, cord-like cell processes are characteristic alterations of the anterior horn cells in familial amyotrophic lateral sclerosis (ALS) with posterior column and spinocerebellar tract involvement. A fine structural analysis of these two structures has been performe...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198409000-00002
更新日期:1984-09-01 00:00:00
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
更新日期:2016-08-01 00:00:00
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
更新日期:2004-03-01 00:00:00
abstract::Since first described, amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of Guam has represented an important model of age-related neurodegenerative disease. ALS/PDC is characterized neuropathologically by severe widespread involvement by neurofibrillary tangles (NFTs). Over the past 30 years there...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/62.4.381
更新日期:2003-04-01 00:00:00
abstract::Placement of a freezing probe on the skull of neonatal rats produces four-layered microgyria, complete with a lamina dissecans and microsulcus. We studied the developmental course of this induced microgyria under light microscopy by examining changes in neurons, glia, and macrophages following a focal freezing insult ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199211000-00005
更新日期:1992-11-01 00:00:00
abstract::The expression of preproenkephalin messenger RNA was studied in the brain of Parkinson disease (PD) patients using in situ hybridization. All these patients were treated with levodopa (LD) and the development of motor complications was recorded. Eleven normal controls and 14 PD patients were used, of which 4 developed...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/61.2.186
更新日期:2002-02-01 00:00:00
abstract::The effects of hypoglycemia on cerebrovascular permeability to a protein, horseradish peroxidase (HRP), were studied in mice given 3 or 8 units of crytalline zinc insulin intraperitoneally. HRP (10 mg in 0.1 ml saline) was injected intravenously 15 to 20 minutes prior to sacrifice. Both mildly and severely hypoglycemi...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198005000-00004
更新日期:1980-05-01 00:00:00
abstract::We studied differences in the number and morphology of parvalbumin-immunoreactive (PV-IR) interneurons in 43 hippocampal specimens from patients with classical Ammon's horn sclerosis (AHS) who underwent anterior temporal lobectomy, as compared with 14 autopsy and non-AHS surgical control specimens. PV-IR neuronal loss...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199709000-00004
更新日期:1997-09-01 00:00:00
abstract::To evaluate cognitive performance among persons who did and did not develop clinical Alzheimer disease (AD) but had AD neuropathology at autopsy, we examined neuropsychological performance in cognitively healthy (Clinical Dementia Rating [CDR] = 0) participants who returned for at least 1 follow-up and died within 2 y...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000254
更新日期:2015-11-01 00:00:00
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
更新日期:2019-01-01 00:00:00
abstract::The association of Charcot-Marie-Tooth (CMT) disease with renal dysfunction is uncommon but has long been recognized in several families. Recently, mutations in the INF2 gene, which encodes inverted formin-2, were identified in patients with focal segmental glomerulosclerosis and a dominant intermediate form of CMT (C...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000047
更新日期:2014-03-01 00:00:00
abstract::Mutations in the cathepsin D (CTSD) gene cause an aggressive neurodegenerative disease (congenital neuronal ceroid lipofuscinosis) that leads to early death. Recent evidence suggests that presynaptic abnormalities play a major role in the pathogenesis of CTSD deficiencies. To identify the early events that lead to syn...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e318238fc28
更新日期:2011-12-01 00:00:00
abstract::The sudden infant death syndrome (SIDS) is the leading cause of postneonatal infant mortality in the United States today, with an overall rate of 0.39/1000 live births. It is defined as the sudden and unexpected death of an infant <12 months of age that remains unexplained after a complete autopsy, death scene investi...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章,评审
doi:10.1093/jnen/nlz062
更新日期:2019-09-01 00:00:00
abstract::Pediatric and NF2-associated meningiomas are uncommon and poorly characterized in comparison to sporadic adult cases. In order to elucidate their molecular features, we analyzed MIB-1, progesterone receptor (PR), NF2, merlin, DAL-1, DAL-1 protein, and chromosomal arms 1p and 14q in 53 meningiomas from 40 pediatric/NF2...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/60.10.994
更新日期:2001-10-01 00:00:00
abstract::A retrospective analysis of 14 patients who presented with a progressively expanding mass lesion(s) shown at biopsy/autopsy to represent acute demyelination was carried out. The aims of this study were to determine the optimal neuropathological approach to diagnosis and to determine the clinical evolution of this cond...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/59.6.477
更新日期:2000-06-01 00:00:00
abstract::Pilocytic astrocytoma (PA) is the most common glioma of childhood. Despite their relatively high incidence, the molecular mechanisms responsible for tumorigenesis and growth of PA are poorly understood. Previous in vitro studies in our laboratory showed that despite the absence of ErbB1, PA was sensitive to ErbB1 tyro...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/01.jnen.0000229989.25171.aa
更新日期:2006-08-01 00:00:00