Abstract:
:Sensitive detection of alpha-synuclein (alpha-syn) pathology is important in the diagnosis of disorders like Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy and in providing better insights into the etiology of these diseases. Several monoclonal antibodies that selectively react with aggregated alpha-syn in pathological inclusions and reveal extensive and underappreciated alpha-syn pathology in the brains of diseased patients were previously reported by Duda et al. (Ann Neurol 52:205-210, 2002). We sought to characterize the specificity of some of these antibodies (Syn 505, Syn 506 and Syn 514); using C-terminal and N-terminal truncations of alpha-syn, all three antibodies were determined to require N-terminal epitopes that minimally comprise amino acids 2-4, but possibly extend to amino acid 12 of alpha-syn. The selectivity of these antibodies was further assessed using biochemical analysis of human brains and reactivity to altered recombinant alpha-syn proteins with duplication variants of amino acids 1-12. In addition, by expressing wild-type or a double mutant (E46K/A53T) of alpha-syn in cultured cells and by comparing their immunoreactivities to another antibody (SNL-4), which has a similar primary epitope, it was determined that Syn 505, Syn 506 and Syn 514 recognize conformational variants of alpha-syn that is enhanced by the presence of the double mutations. These studies indicate that antibodies Syn 505, Syn 506 and Syn 514 preferentially recognize N-terminal epitopes in complex conformations, consistent with the dramatic conformational change associated with the polymerization of alpha-synuclein into amyloid fibrils that form pathological inclusions.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Waxman EA,Duda JE,Giasson BIdoi
10.1007/s00401-008-0375-1subject
Has Abstractpub_date
2008-07-01 00:00:00pages
37-46issue
1eissn
0001-6322issn
1432-0533journal_volume
116pub_type
杂志文章abstract::Twenty necropsy cases of the association of fetal encephalitis with porencephaly, hydranencephaly or polymicrogyria were reviewed including 5 from the authors' material. The latter include a basket brain, a porencephalic necrosis of recent date and a polymicrogyria in the formative state. The supratentorial lesions ar...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00685011
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abstract::Motor neuron disease (MND) may be complicated by frontotemporal dementia and/or an extrapyramidal movement disorder. Several studies have identified the pathological substrate for dementia in MND as being ubiquitin-immunoreactive inclusions and dystrophic neurites in the extramotor neocortex and hippocampus. Although ...
journal_title:Acta neuropathologica
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doi:10.1007/s00401-003-0814-y
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abstract::Hyper- and hypothyroidism repercussions on soma, nucleus and cytoplasm increases were studied by electron microscopy on 7-, 14-, 21-, and 35-day-old rats. Adult normal animals were compared with adult ones made hypothyroid until they were 35 days old. Also heat value restriction of food intake effects were compared wi...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:
更新日期:1978-09-15 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050395
更新日期:1996-01-01 00:00:00
abstract::Neuronal accumulation of oligomeric amyloid-beta (Alphabeta) is considered the proximal cause of neuronal demise in Alzheimer disease (AD) patients. Blood-borne macrophages might reduce Abeta stress to neurons by immigration into the brain and phagocytosis of Alphabeta. We tested migration and export across a blood-br...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-008-0481-0
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abstract::Progressive myopathy developed in two women who consumed ipecac syrup containing emetine hydrochloride to induce vomiting as part of their anorexia nervosa. Muscle biopsy specimens were characterized by severe disruption of the sarcomeres. The ultrastructural spectrum extended from "Z-band streaming" to the formation ...
journal_title:Acta neuropathologica
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doi:10.1007/BF00686202
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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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doi:10.1007/BF00684666
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010000296
更新日期:2001-04-01 00:00:00
abstract::Synucleinopathies, such as Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), are defined by the presence of α-synuclein (αSYN) aggregates throughout the nervous system but diverge from one another with regard to their clinical and pathological phenotype. The recent generatio...
journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
pub_type: 历史文章,杂志文章,评审
doi:10.1007/s00401-007-0200-2
更新日期:2007-05-01 00:00:00
abstract::This paper examines the neuropathology of oxygen-glucose deprivation uncomplicated by stagnant conditions. Rabbit vagus nerves were pulled into a multi-compartment perfusion chamber, stimulated five times per second and deprived of energy by substituting nitrogen and deoxyglucose for oxygen and glucose in the Locke's ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00685378
更新日期:1982-01-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-003-0781-3
更新日期:2004-02-01 00:00:00
abstract::The spatial patterns of diffuse, primitive, classic (cored) and compact (burnt-out) subtypes of beta/A4 deposits were studied in coronal sections of the frontal lobe and hippocampus, including the adjacent gyri, in nine cases of Alzheimer's disease (AD). If the more mature deposits were derived from the diffuse deposi...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00454896
更新日期:1993-01-01 00:00:00
abstract::Upon brain reperfusion following ischemia, there is widespread inhibition of neuronal protein synthesis that is due to phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha), which persists in selectively vulnerable neurons (SVNs) destined to die. Other investigators have shown that expression of mutant eI...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-003-0693-2
更新日期:2003-07-01 00:00:00
abstract::New pericapillary inclusion bodies were found in 17 cases of sporadic amyotrophic lateral sclerosis (ALS). The inclusion bodies consisted of paracrystalline arrays with 5-7 nm electron-dense subunits, were discernible with the light microscope and had the staining properties of protein. They were surrounded by capilla...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687970
更新日期:1986-01-01 00:00:00
abstract::X-linked adrenoleukodystrophy (X-ALD) is a rare neurometabolic disease characterized by the accumulation of very long chain fatty acids (VLCFAs) due to a loss of function of the peroxisomal transporter ABCD1. Here, using in vivo and in vitro models, we demonstrate that autophagic flux was impaired due to elevated mamm...
journal_title:Acta neuropathologica
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doi:10.1007/s00401-014-1378-8
更新日期:2015-03-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-019-02067-z
更新日期:2020-01-01 00:00:00
abstract::With an incidence of approximately 350 in 100,000, stroke is the third leading cause of death and a major cause of disability in industrialized countries. At present, although progress has been made in understanding the molecular pathways that lead to ischemic cell death, the current clinical treatments remain poorly ...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/s00401-009-0496-1
更新日期:2009-05-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688122
更新日期:1985-01-01 00:00:00
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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doi:10.1007/BF00687775
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00296520
更新日期:1995-01-01 00:00:00
abstract::Pediatric glioblastomas (GBM) including diffuse intrinsic pontine gliomas (DIPG) are devastating brain tumors with no effective therapy. Here, we investigated clinical and biological impacts of histone H3.3 mutations. Forty-two DIPGs were tested for H3.3 mutations. Wild-type versus mutated (K27M-H3.3) subgroups were c...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-012-0998-0
更新日期:2012-09-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00318572
更新日期:1995-01-01 00:00:00
abstract::We described the first two unrelated Polish families with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). In the morphological examination with light microscopy, two kinds of changes were observed: (1). panarteritis nodosa-like changes with eosinophilic fibrinoid n...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-003-0764-4
更新日期:2003-12-01 00:00:00
abstract::Aim of the present study was to establish different immunohistochemical staining patterns for a subsequent comparison with those of primitive neuroectodermal (PNET) subsets, i.e. PNET-NOS (not otherwise specified) or PNET with focal neuronal, astrocytic or ependymal differentiation, to relate neoplastic to embryonal d...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00293385
更新日期:1991-01-01 00:00:00
abstract::Seven patients aged 29 to 76 years with various clinical subtypes of chronic inflammatory demyelinating polyneuropathy (CIDP) were investigated. Sural nerve biopsies were performed between 7 months and 19 years after onset of disease. Quantitative electron microscopy revealed involvement of primary unmyelinated fibers...
journal_title:Acta neuropathologica
pub_type: 杂志文章
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00685343
更新日期:1983-01-01 00:00:00
abstract::Previous investigators have suggested that proteolysis by calpain, a Ca2+-dependent protease, causes muscle fiber degradation in Duchenne and Becker muscular dystrophies (DMD/BMD). Recent evidence indicates that the nonlysosomal ATP-ubiquitin-dependent proteolytic complex (proteasomes) participates in muscle wasting d...
journal_title:Acta neuropathologica
pub_type: 杂志文章
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更新日期:2000-12-01 00:00:00