Abstract:
:Although it is known that deletions or mutations of the SMN1 gene on chromosome 5 cause decreased levels of the SMN protein in subjects with proximal autosomal recessive spinal muscular atrophy (SMA), the exact sequence of pathological events leading to selective motoneuron cell death is not fully understood yet. In this review, new findings regarding the dual cellular role of the SMN protein (translocation of beta-actin to axonal growth cones and snRNP biogenesis/pre-mRNA splicing) were integrated with recent data obtained by detailed neuropathological examination of SMA and control subjects. A presumptive series of 10 pathogenetic events for SMA is proposed as follows: (1) deletions or mutations of the SMN1 gene, (2) increased SMN mRNA decay and reduction in full-length functional SMN protein, (3) impaired motoneuron axono- and dendrogenesis, (4) failure of motoneurons to form synapses with corticospinal fibers from upper motoneurons, (5) abnormal motoneuron migration towards ventral spinal roots, (6) inappropriate persistence of motoneuron apoptosis due to impaired differentiation and motoneuron displacement, (7) substantial numbers of motoneurons continuing to migrate abnormally ("heterotopic motoneurons") and entering into the ventral roots, (8) attracted glial cells following these heterotopic motoneurons, which form the glial bundles of ventral roots, (9) impaired axonal transport of actin, causing remaining motoneurons to become chromatolytic, and (10) eventual death of all apoptotic, heterotopic and chromatolytic neurons, with apoptosis being more rapid and predominating in the earlier stages, with death of heterotopic and chromatolytic neurons occurring more slowly by necrosis during the later stages of SMA. According to this model, the motoneuron axonopathy is more important for pathogenesis than the ubiquitous nuclear splicing deficit. It is also supposed that individually variable levels of SMN protein, together with influences of other phenotype modifier genes and their products, cause the clinical SMA spectrum through differential degree of motoneuron functional loss.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Simic Gdoi
10.1007/s00401-008-0411-1subject
Has Abstractpub_date
2008-09-01 00:00:00pages
223-34issue
3eissn
0001-6322issn
1432-0533journal_volume
116pub_type
杂志文章,评审abstract::A mixed lymphoblastic T cell lymphoma and gonadotroph cell pituitary adenoma occurred 25 years after first resection of the adenoma. Within 1 year the lymphoma overgrew the adenoma, but was still restricted to the sellar region. Histologically, lymphoma and adenoma components were tightly admixed. Possible pathogeneti...
journal_title:Acta neuropathologica
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doi:10.1007/s004010050990
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abstract::Investigations of the existence and distribution of muscle spindles and tendon organs in the human voluntary anal sphincter muscle in 53 cases of autopsy material from both female and male persons (age: 27th week of gestation to 81 years) brought forward the following results: Similar to animals, muscle spindles are f...
journal_title:Acta neuropathologica
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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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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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abstract::A quantitative technique involving serial sectioning and semiautomatic morphometric analysis was used to assess the severity of the reduction in size of the major brain structures in cerebral hemispheres of children congenitally infected with HIV-1. Cerebral hemispheres from 12 children (18-48 months of age) who died ...
journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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更新日期:2011-02-01 00:00:00
abstract::The dynamics of cell-associated Concanavalin A (Con A) in astrocytes of the newborn rat (RNA), the rat glioma (AC), and the human glioblastoma (GB) were studied in vitro by fluorescence and electron microscopy. Con A receptors on the cell surface were seen usually as a continuous thin layer, and Con A accumulations in...
journal_title:Acta neuropathologica
pub_type: 杂志文章
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更新日期:1982-01-01 00:00:00
abstract::The alterations in oligodendrocytes in myelin basic protein-induced acute experimental autoimmune encephalomyelitis (EAE) in the Lewis rat were studied using the technique of pre-embedding immunolabelling with the Rip monoclonal antibody, which specifically labels the cytoplasm of the cell bodies and processes of olig...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050763
更新日期:1998-01-01 00:00:00
abstract::Behaviour of biogenic amines was studied in the brains of Mongolian gerbils subjected to unilateral occlusion of the common carotid artery. Assays on the hemispheres ipsilateral to occlusion revealed in symptom-positive animals a progressive decrease in norepinephrine and dopamine, and an increase in serotonin through...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00685142
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abstract::Pelizaeus-Merzbacher disease (PMD) is an untreatable and fatal leukodystrophy. In a model of PMD with perturbed blood-brain barrier integrity, cholesterol supplementation promotes myelin membrane growth. Here, we show that in contrast to the mouse model, dietary cholesterol in two PMD patients did not lead to a major ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
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更新日期:2019-07-01 00:00:00
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
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abstract::Three cases of spinal tanycytic ependymoma are reported, a man aged 45 years and two women aged 36 and 55 years. Each patient developed gradual paraparesis over a few months prior to admission. Magnetic resonance imaging showed an enhancing, well-circumscribed tumor in the spinal cord in each case. Histologically, the...
journal_title:Acta neuropathologica
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更新日期:2001-01-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687036
更新日期:1986-01-01 00:00:00
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journal_title:Acta neuropathologica
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abstract::There is evidence that apoptotic cell death mechanisms contribute to muscle fibre loss in dystrophinopathies, but little knowledge about the activators of the final degrading caspase cascade in muscle fibre apoptosis. As mitochondria-related activation of this caspase cascade, through e.g. APAF-1, could not be proven ...
journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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abstract::Defects of major histocompatibility complex (MHC) class I antigen-processing machinery (APM) components have been shown to contribute to immune escape of malignant cells. We investigated the expression of APM components in astrocytomas without detectable defects in HLA class I antigen expression and correlated it with...
journal_title:Acta neuropathologica
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更新日期:2007-08-01 00:00:00
abstract::Endoneurial cell response and type of nerve fibre damage were studied after perineural injections of 7% phenol-aqua and pure glycerol. Our previous studies have shown that phenol and glycerol induce different types of nerve fibre degeneration after intraneural injections: phenol dissolves axons and Schwann cells insid...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-004-0896-1
更新日期:2004-10-01 00:00:00
abstract::The neuropathologic findings in the brain of a National Aeronautics and Space Administration (NASA) engineer, who died subsequent to nitrogen inhalation, are reported. Findings which are unusual in other forms of anoxia included relative preservation of neurons in the Sommer sector of the hippocampus and a pattern of ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
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abstract::A case of secretory meningioma with numerous meningothelial rosettes is reported. A 66-year-old man with moyamoya disease gradually developed skull deformity, and underwent surgery for the skull tumor overlying the hemisphere. Histological examination disclosed numerous meningothelial rosettes quite similar to those i...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00227831
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abstract::Immunohistochemical techniques were employed to examine the changes in free ubiquitin within the hippocampus 1, 3, 7, 14, and 30 days after a unilateral perforant pathway lesion occurred in the rat brain. Immunoreactivity for ubiquitin was remarkably decreased in the cell body and proximal dendrites of neurons through...
journal_title:Acta neuropathologica
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abstract::Double immunofluorescence for paired helical filament (PHF)-tau (AT8) and ubiquitin, enhanced by catalyzed reporter deposition amplification, was combined with thiazin red (TR), a fluorochrome, which has an affinity to fibrillary structures such as neurofibrillary tangles (NFTs). After recording these triple-fluoresce...
journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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更新日期:2000-09-01 00:00:00
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更新日期:2003-07-01 00:00:00