Abstract:
:The calcium-activated protease calpain cleaves a variety of biologically important proteins and serves, therefore, as a key regulator of many cellular functions. Activation of both main isoforms, calpain 1 and calpain 2, was demonstrated previously in Alzheimer's disease. In this report, antibodies specifically recognizing the active form of calpain 2 were used to investigate calpain 2 activation in a broad range of neurodegenerative diseases, utilizing multiple-label confocal immunofluorescence imaging. With rare exceptions, the active form of calpain 2 was found in colocalization with hyperphosphorylated tau protein. Aggregates of mutated huntingtin, alpha-synuclein, or unidentified protein in motor neuron disease type of frontotemporal dementia were always negative. These findings indicate that calpain 2 activation is not a general response to protein aggregation. In tauopathies, more pathological inclusions were labeled for hyperphosphorylated tau than for activated calpain 2. The extent of colocalization varied in both a disease-specific and cell-type specific manner. The active form of calpain 2 was detected in 50-75% of tau neurofibrillary pathology in Alzheimer's disease, Alzheimer neurofibrillary changes and Down's syndrome, as well as in the accompanying Alzheimer-type tau pathology in diffuse Lewy bodies disease, progressive supranuclear palsy, and corticobasal degeneration. For glial cells, only 10-25% of tuft-shaped astrocytes, glial plaques, or coiled bodies contained activated calpain 2. The majority of Pick bodies were negative. The association of calpain 2 activation with hyperphosphorylated tau might be the result of an attempt by the calpain proteolytic system to degrade the tau protein aggregates. Alternatively, calpain 2 could be directly involved in tau hyperphosphorylation by modulating protein kinase activities. Overall, these results provide evidence of the important role of the calpain proteolytic system in the pathogenesis of neurodegenerative diseases with tau neurofibrillary pathology.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Adamec E,Mohan P,Vonsattel JP,Nixon RAdoi
10.1007/s00401-002-0528-6subject
Has Abstractpub_date
2002-07-01 00:00:00pages
92-104issue
1eissn
0001-6322issn
1432-0533journal_volume
104pub_type
杂志文章abstract::Experimental allergic neuritis (EAN) was induced in normal and irradiated Lewis rats by passively transferring T cells sensitized to SP-26, a peptide fragment of P2 myelin protein. The recipients became sick 4-8 days post transfer and the degree of disability correlated directly with the dose of T cells. Smaller doses...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00294298
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abstract::Specific pathological hallmarks have been described in amyotrophic lateral sclerosis (ALS), which include motor neuronal loss, Bunina bodies (BBs) and skein like inclusions (SLIs). We investigated the relation between these three lesions in the cervical and lumbar anterior horns and the hypoglossal nuclei of 20 ALS pa...
journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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abstract::The fine structure of an intracerebellar "fibroma" has been examined. The tumor consists of irregularly-shaped cells connected by well developed junctional complexes. Unusual, fenestrated capillaries with extremely narrow and irregular lumens are frequent. Collagen fibers are not common but the wide extracellular spac...
journal_title:Acta neuropathologica
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abstract::A murine model of Tay-Sachs disease, the prototype of the GM2 gangliosidoses, was produced through the targeted disruption of the Hexa gene encoding the subunit of alpha-hexosaminidase A. The mice were completely devoid of beta-hexosaminidase A activity and accumulated GM2 ganglioside in the CNS in an age-dependent ma...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00309622
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abstract::A 25-year-old homosexual AIDS patient presented with progressive cognitive, motor and behavioral disturbances consistent with HIV encephalopathy. CT scans demonstrated progressive diffuse brain atrophy. Neuropathology showed predominant cortical changes including severe neuronal loss corroborated by morphometry. Only ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00294450
更新日期:1991-01-01 00:00:00
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00293394
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journal_title:Acta neuropathologica
pub_type: 杂志文章
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更新日期:1982-01-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
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更新日期:2017-11-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00686206
更新日期:1988-01-01 00:00:00
abstract::The extent of DNA fragmentation analysed using the TUNEL technique was evaluated in post-mortem human brain tissue. Twenty-four patients with clinical and histopathological diagnosis of Alzheimer's disease (AD) and a short post-mortem delay were analysed. We report an increase in the count of TUNEL-labelled cells as t...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010000228
更新日期:2000-12-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00692870
更新日期:1980-01-01 00:00:00
abstract::A 56-day-old infant with alpha-neuraminidase deficiency, whose clinical features included severe edema of extremities and ascites which resembled those in severe infantile sialidosis, was autopsied. Perforation, whose pathogenesis was unclear, was found on the descending portion of the duodenum. Light and electron mic...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688050
更新日期:1986-01-01 00:00:00
abstract::The morphology of toxoplasma and its interaction with the cellular elements of the brain were studied in a patient who dies of extensive cerebral toxoplasmosis superimposed on Hodgkin's disease. The cerebral lesions were devoid of inflammatory cellular response and contained numerous organisms mostly in isolated multi...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690360
更新日期:1978-06-30 00:00:00
abstract::Aberrant peripheral nerve fiber bundles, i.e., masses of peripheral nerve fibers without perineural sheath cells, are found in the perivascular spaces of some spinal cords. The 514 spinal cords examined for these structures were separated into two groups; 507 spinal cords without definite necrotic lesions (group 1) an...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00308951
更新日期:1989-01-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-008-0375-1
更新日期:2008-07-01 00:00:00
abstract::The original version of this article unfortunately contained a typesetting error in Fig 3c. The corrected Fig. 3 is given in the following page. ...
journal_title:Acta neuropathologica
pub_type: 杂志文章,已发布勘误
doi:10.1007/s00401-019-02115-8
更新日期:2020-02-01 00:00:00
abstract::The ultrastructure of the nervous tissue in a benign ovarian teratoma is described. This tissue was organized into areas having both "meningeal" and "ependymal" surfaces, between which were found astrocytes, ependymal cells, neurones with synapses and microglia. These cells all had ultrastructural similarities to thei...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00686623
更新日期:1987-01-01 00:00:00
abstract::Defective interfering influenza virus particles lessened the yield of infective virus recovered from brain after intracerebral challange of 3-week old mice, but failed to affect the appearance of disease or lethality. In 7-week old mice, the presence of defective interfering influenza virus particles reduced both leth...
journal_title:Acta neuropathologica
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abstract::It is well established that the binding of pathogenic aquaporin-4 (AQP4)-specific autoantibodies to astrocytes may initiate a cascade of events culminating in the destruction of these cells and in the formation of large tissue-destructive lesions typical for patients with neuromyelitis optica spectrum disorders (NMOSD...
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journal_title:Acta neuropathologica
pub_type: 杂志文章
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abstract::Six medulloblastomas were studied by electron microscopy. Two features were found which seem to be constant and essential characteristics of medulloblastoma. First, cell junctions are abundant between tumor cells. These are mostly desmosome-like but other, closer junctions, were also seen. Second, the capillary endoth...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00685966
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abstract::Patients with von Hippel-Lindau disease carry a germline mutation of the Von Hippel-Lindau (VHL) tumor-suppressor gene. We discuss the molecular consequences of loss of VHL gene function and their impact on the nervous system. Dysfunction of the VHL protein causes accumulation and activation of hypoxia inducible facto...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688340
更新日期:1987-01-01 00:00:00
abstract::Six subtypes of sporadic Creutzfeldt-Jakob disease with distinctive clinico-pathological features have been identified largely based on two types of the abnormal prion protein, PrP(Sc), and the methionine (M)/valine (V) polymorphic codon 129 of the prion protein. The existence of affected subjects showing mixed phenot...
journal_title:Acta neuropathologica
pub_type: 杂志文章
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更新日期:2009-11-01 00:00:00
abstract::The spinal cord of 20 patients with amyotrophic lateral sclerosis (ALS) and 5 patients with lower motor neuron disease (LMND) were investigated immunohistochemically using anti-human excitatory amino acid transporter 1 (EAAT1) and EAAT2 antibodies which are the astrocytic transporters. The purpose of the study was to ...
journal_title:Acta neuropathologica
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更新日期:2000-08-01 00:00:00
abstract::Severe hypoxic-ischemic cerebral damage was produced in 8-day-old rats following permanent bilateral carotid artery occlusion and 15 min of ischemia. Cellular damage consisted of early necrosis and appearance of cells with apoptotic-like morphology (karyorrhectic cells) and cells with granular chromatin degeneration i...
journal_title:Acta neuropathologica
pub_type: 杂志文章
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更新日期:1997-12-01 00:00:00
abstract::The paper describes the clinical and morphological features of a congenital neurological disease affecting two in-bred litter-mate kittens. The principal neurological features were ataxia and dysmetria. In one of the kittens light microscopy revealed widespread vacuolation of white and grey matter of the brain and spi...
journal_title:Acta neuropathologica
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