Abstract:
AIMS:Granulovacuolar degeneration involves the accumulation of large, double membrane-bound bodies within certain neurones during the course of Alzheimer's disease (AD) and other adult-onset dementias. Because of the two-layer membrane morphology, it has been proposed that the bodies are related to autophagic organelles. The aim of this study was to test this hypothesis, and determine the approximate stage at which the pathway stalls in AD. METHODS:Spatial colocalization of autophagic and endocytic markers with casein kinase 1 delta, a marker for granulovacuolar degeneration (GVD) bodies, was evaluated in hippocampal sections prepared from post mortem Braak stage IV and V AD cases using double-label confocal fluorescence microscopy. RESULTS:GVD bodies colocalized weakly with early-stage autophagy markers LC3 and p62, but strongly with late-stage marker lysosome-associated membrane protein 1 (LAMP1), which decorated their surrounding membranes. GVD bodies also colocalized strongly with charged multivesicular body protein 2B (CHMP2B), which colocalized with the core granule, but less strongly with lysosomal marker cathepsin D. CONCLUSIONS:The resultant immunohistochemical signature suggests that granulovacuolar degeneration bodies (GVBs) do contain late-stage autophagic markers, and accumulate at the nexus of autophagic and endocytic pathways. The data further suggest that failure to complete autolysosome formation may be an important correlate of GVB accumulation.
journal_name
Neuropathol Appl Neurobioljournal_title
Neuropathology and applied neurobiologyauthors
Funk KE,Mrak RE,Kuret Jdoi
10.1111/j.1365-2990.2010.01135.xsubject
Has Abstractpub_date
2011-04-01 00:00:00pages
295-306issue
3eissn
0305-1846issn
1365-2990journal_volume
37pub_type
杂志文章abstract:AIMS:EphB2 is a member of receptor tyrosine kinases (RTKs) family that is essential for the cell adhesion, neural crest migration, axon guidance and synaptogenesis in the nervous system. Recent studies show that preservation of EphB2 in a transgenic mouse model of Alzheimer's disease (AD) rescues the cognitive deficit,...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12019
更新日期:2013-10-01 00:00:00
abstract::Mitochondrial dysfunction leads to oxygen free radical (ROS) generation with consequent oxidative stress and cellular damage. Recently, activation of the cellular antioxidant system and apoptosis were demonstrated in skeletal muscle fibres from patients with mitochondrial diseases, but the underlying mechanisms remain...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2003.00411.x
更新日期:2003-02-01 00:00:00
abstract::Immunohistochemistry using antibodies to dystrophin is the pathological basis for the diagnosis of Duchenne and Becker muscular dystrophy (DMD and BMD). While the sarcolemma of DMD muscle is negative, BMD muscle generally shows variable labelling because of the translation of a partially functional dystrophin that is ...
journal_title:Neuropathology and applied neurobiology
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doi:10.1111/j.1365-2990.2004.00561.x
更新日期:2004-10-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a fatal devastating neurodegenerative disorder which predominantly affects the motor neurons in the brain and spinal cord. The death of the motor neurons in ALS causes subsequent muscle atrophy, paralysis and eventual death. Clinical and biological evidence now demonstrates that ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/nan.12206
更新日期:2015-08-01 00:00:00
abstract::Neuronal loss is often quoted as an element of the pathology of the transmissible spongiform encephalopathies, but few data are published. To determine whether neuronal loss is a salient feature of murine scrapie, and whether there is a relationship with the other hallmark lesions of scrapie we compared the numbers of...
journal_title:Neuropathology and applied neurobiology
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doi:10.1111/j.1365-2990.1995.tb01027.x
更新日期:1995-02-01 00:00:00
abstract::Pathologists have been establishing archives of human organs and tissue for research use for many years now. Controversy has arisen recently over these collections, particularly with regard to the right of patients or relatives to consent to removal and retention of tissue, genetic research using stored tissue samples...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2990.2000.00276.x
更新日期:2000-10-01 00:00:00
abstract::This paper continues the historical review on the concept of a sensorimotor cortex into the twentieth century. Paul Flechsig was probably the first to accept this concept after the turn of the century. Like Munk, he believed in an almost reflex-like unity between cortical sensory and motor function. With the help of h...
journal_title:Neuropathology and applied neurobiology
pub_type: 历史文章,杂志文章
doi:10.1111/j.1365-2990.1982.tb00264.x
更新日期:1982-03-01 00:00:00
abstract::Accumulating evidence indicates an important pathophysiological role of brain inflammation in epilepsy. In this review, we will provide an update of specific inflammatory pathways that have been proposed to be crucial in the underlying molecular mechanisms of epilepsy, including the interleukin-1 receptor/toll-like re...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/nan.12444
更新日期:2018-02-01 00:00:00
abstract::Transmissible mink encephalopathy (TME) is probably a form of the sheep disease, scrapie, introduced by accidentally feeding mink with scrapie-infected sheep tissues. Although no successful transmissions of TME to mice have been achieved previous work has involved various limitations. To maximize the possibility of tr...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1986.tb00051.x
更新日期:1986-03-01 00:00:00
abstract::During an electron microscopic study of the white matter in multiple sclerosis (MS), spheroidal reticular particles were found both in MS and in control brains. These particles have previously been described in the brain in MS and in brain-derived cell cultures in subacute sclerosing panencephalitis. In both cases the...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1978.tb01347.x
更新日期:1978-09-01 00:00:00
abstract::Serial sections of the brains of two cases with Alzheimer's disease were stained with the standard Bodian, modified Bielschowsky (reformed Gros-Schultze's modification) and thioflavin S methods. The numbers of demonstrated Alzheimer's neurofibrillary tangles (NFTs) were different between the two silver stains: from 15...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1986.tb00677.x
更新日期:1986-01-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of upper and lower motor neurones leading to muscle weakness and paralysis. Despite recent advances in the genetics of ALS, the mechanisms underlying motor neurone degeneration are not fully understood. Mitochondria are know...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2990.2011.01166.x
更新日期:2011-06-01 00:00:00
abstract:AIMS:Although modifications of the survival motor neurone gene are responsible for most spinal muscular atrophy (SMA) cases, the molecular pathophysiology and the muscular target proteins involved are still unknown. The aim of this study was to compare the expression of contractile and regulatory protein isoforms in qu...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2008.00950.x
更新日期:2008-12-01 00:00:00
abstract::Mutations in the tau gene cause familial frontotemporal dementia with parkinsonism linked to chromosome 17 characterized by filamentous tau protein deposits. Here we describe the clinical and neuropathological features of a case from a newly identified family with an intron 10+3-splice site mutation in the tau gene. T...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2005.00629.x
更新日期:2005-08-01 00:00:00
abstract:AIMS:Plectin, a universally expressed multi-functional cytolinker protein, is crucial for intermediate filament networking, including crosstalk with actomyosin and microtubules. In addition to its involvement in a number of diseases affecting skin, skeletal muscle, heart, and other stress-exposed tissues, indications f...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12635
更新日期:2021-02-01 00:00:00
abstract:AIMS:Nakajo-Nishimura syndrome (NNS) is an autosomal recessive disease caused by biallelic mutations in the PSMB8 gene that encodes the immunoproteasome subunit β5i. There have been only a limited number of reports on the clinicopathological features of the disease in genetically confirmed cases. METHODS:We studied cl...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12614
更新日期:2020-10-01 00:00:00
abstract::Mice and rats are found to be equally susceptible to developing symmetrical brain stem lesions on exposure to alpha-chlorohydrin and in both species the earliest neurotoxic changes are strictly confined to glial cells, particularly astrocytes; haemorrhages are not found in either species. Minimal evidence of increased...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1993.tb00434.x
更新日期:1993-06-01 00:00:00
abstract::Vascular endothelial growth factor (VEGF) is an angiogenic factor essential for the formation of new blood vessels during embryogenesis and in many pathological conditions. A new role for VEGF as a neurotrophic factor has recently emerged. In the developing nervous system, VEGF plays a pivotal role not only in vascula...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2990.2004.00600.x
更新日期:2004-10-01 00:00:00
abstract:AIMS:We observed a microvascular structure in the cerebral cortex that has not, to our knowledge, been previously described. We have termed the structure a 'raspberry', referring to its appearance under a bright-field microscope. We hypothesized that raspberries form through angiogenesis due to some form of brain ischa...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12552
更新日期:2019-10-01 00:00:00
abstract::Alzheimer's and Parkinson's diseases (AD, PD) are among the most common neurodegenerative disorders in adults. Both AD and PD have a complex aetiology, and it is widely considered that genetic factors, acting independently or in concert with other genetic and/or environmental factors, modify the risk of developing the...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:
更新日期:1997-08-01 00:00:00
abstract::The pattern of cell loss and neuronal degeneration resulting from multiple microinjections of N-methyl-D-aspartate (NMDA), ibotenate (IBO), quisqualate (QUIS), and kainate (KA) into hippocampus was studied, together with the protection provided by the NMDA antagonist 3-(+/-)-2-carboxypiperazin-4-yl-propyl-1-phosphonat...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1993.tb00458.x
更新日期:1993-10-01 00:00:00
abstract::Rats were given 2,5-hexanediol in their water for more than 5 weeks. The changes in the optic pathways were studied both qualitatively and quantitatively. Increase in 10-nm filaments within axons was noticeable from 10 days onwards in the superior colliculus and in the brachium of the superior colliculus. From then on...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1982.tb00298.x
更新日期:1982-07-01 00:00:00
abstract::Changes of 5'-nucleotidase (5'-N) activity during subcultivation of C6 clonal rat glioma cells were studied histochemically, cytochemically and biochemically. Two different cell populations were seeded with high or low cell density respectively. 5'-N activity in cultured cells increased continuously in both population...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1985.tb00014.x
更新日期:1985-05-01 00:00:00
abstract:AIM:To understand the progression of CLN1 disease and develop effective therapies we need to characterize early sites of pathology. Therefore, we performed a comprehensive evaluation of the nature and timing of early CLN1 disease pathology in the spinal cord, which appears especially vulnerable, and how this may affect...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12658
更新日期:2020-08-25 00:00:00
abstract::Two cases are described, one with a multifocal cranial and limb neuropathy of adult onset associated with optic neuropathy, and the other with a diffuse demyelinating neuropathy characterized by congenital cataract, mental retardation and progressive lower limb paresis with an onset in childhood. Extensive investigati...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.0305-1846.2000.00289.x
更新日期:2000-12-01 00:00:00
abstract:AIMS:Brain mural cells (BMC), smooth muscle cells and pericytes, interact closely with endothelial cells and modulate numerous cerebrovascular functions. A loss of BMC function is suspected to play a role in the pathophysiology of Alzheimer's Disease (AD). METHODS:BMC markers, namely smooth muscle alpha actin (α-SMA) ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12599
更新日期:2020-08-01 00:00:00
abstract:OBJECTIVE:To perform a systematic review and meta-analysis on the prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults. METHODS:We systematically reviewed and performed a meta-analysis on the prevalence of TDP-43 proteinopathy in older adults with normal c...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,meta分析
doi:10.1111/nan.12430
更新日期:2018-04-01 00:00:00
abstract:AIMS:14,15-Epoxyeicosatrienoic acid (14,15-EET) is abundantly expressed in brain and exerts protective effects against ischaemia. 14,15-EET is hydrolysed by soluble epoxide hydrolase (sEH). sEH-/- mice show a higher level of 14,15-EET in the brain. Astrocytes play a pivotal role in neuronal survival under ischaemic con...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12291
更新日期:2016-12-01 00:00:00
abstract::Two cases of Aspergillus infection of the nervous system are reported. In the first case it occurred in a healthy individual and presented as a space occupying lesion mimicking a tuberculous granuloma. In the second case it was an opportunistic infection in a patient with predisposing conditions and manifested as chro...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1983.tb00131.x
更新日期:1983-11-01 00:00:00
abstract::Prolonged neurotoxicity of the recreational drug, MDMA (3,4-methylenedioxymethamphetamine) on serotoninergic axon terminals has been suggested. The effect of a single (15 mg/kg) dose of intraperitoneally administered MDMA on serotoninergic fibre density, defined by tryptophan hydroxylase (TpH) and serotonin transporte...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2006.00790.x
更新日期:2007-04-01 00:00:00