Abstract：
:Disturbance of intracellular trafficking plays a major role in several neurodegenerative disorders including Alzheimer or Parkinson's disease. The Chediak-Higashi syndrome (CHS), a life-threatening autosomal recessive disease with frequent mutations in the LYST gene, and its animal model, the beige mouse, are both characterized by lysosomal defects with accumulation of giant lysosomes. Clinically they manifest as hypopigmentation, abnormal bleeding and increased susceptibility to infection with various degrees of involvement of the nervous system. In the course of a recessive N-ethyl-N-nitrosurea (ENU) mutagenesis screen, we identified the first murine missense mutation in the lysosomal trafficking regulator gene (Lyst(Ing3618)) located at a highly conserved position in the WD40 protein domain. Nearly all described human Lyst alleles lead to protein truncation and fatal childhood CHS. Only four different missense mutations have been reported in patients with adolescent or adult forms of CHS involving the nervous system. Interestingly, the Lyst(Ing3618) model presents with a predominant neurodegenerative phenotype with progressive degeneration and loss of Purkinje cells and lacks severe impairment of the immune system. Therefore, the Lyst(Ing3618 )allele could represent a new model for adult CHS with neurological impairment. It could also provide an important tool to elucidate the role of neuronal lysosomal trafficking in the pathophysiology of neurodegeneration.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Rudelius M,Osanger A,Kohlmann S,Augustin M,Piontek G,Heinzmann U,Jennen G,Russ A,Matiasek K,Stumm G,Schlegel Jdoi
10.1007/s00401-006-0092-6subject
Has Abstractpub_date
2006-09-01 00:00:00pages
267-76issue
3eissn
0001-6322issn
1432-0533journal_volume
112pub_type
杂志文章abstract：:We described a new type of cytoplasmic inclusion in the choroidal epithelial cells of humans. The inclusions usually appeared as brown, round or elongated bodies with or without an inner core, ranging in size from 1.3 to 7.0 micron. Histochemically, they contained polysaccharides, proteins and compound lipids. Ultrast...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687675
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abstract：:Lysolecithin has been used in many studies to induce demyelination in peripheral nerves. In the present investigation lysolecithin (lysophosphatidyl choline) was injected into rat sciatic nerves at a dose of 2-3 microns of a 10 mg/ml solution in order to study the effects of this lipid on cellular elements other than ...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00690634
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journal_title：Acta neuropathologica
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doi：10.1007/BF00685966
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journal_title：Acta neuropathologica
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doi：10.1007/BF00230493
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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/BF00690379
更新日期：1977-07-15 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
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journal_title：Acta neuropathologica
pub_type： 杂志文章
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journal_title：Acta neuropathologica
pub_type： 杂志文章
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更新日期：1979-03-15 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：2000-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-011-0906-z
更新日期：2012-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00294292
更新日期：1993-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010051012
更新日期：1999-05-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-017-1797-4
更新日期：2018-02-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/pl00007398
更新日期：1997-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s00401-003-0771-5
更新日期：2004-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688637
更新日期：1985-01-01 00:00:00
abstract：:Neuronal intracytoplasmic inclusions were found in the ventrolateral and posterior nuclei of the thalamus of 3-month-old thiamine-deficient mice and quaking mice. An electron-microscopic study revealed that these inclusions were composed of condensation of parallel rectilinear 10-nm filaments with interconnecting cros...
journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00691499
更新日期：1983-01-01 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：2013-05-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/s004010050856
更新日期：1998-07-01 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：2005-12-01 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：1996-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00227831
更新日期：1992-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00296486
更新日期：1994-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00311392
更新日期：1992-01-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00688632
更新日期：1985-01-01 00:00:00
abstract：:α-Synuclein (αSyn) histopathology defines several neurodegenerative disorders, including Parkinson's disease, Lewy body dementia, and Alzheimer's disease (AD). However, the functional link between soluble αSyn and disease etiology remains elusive, especially in AD. We, therefore, genetically targeted αSyn in APP trans...
journal_title：Acta neuropathologica
pub_type： 杂志文章
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更新日期：2018-10-01 00:00:00
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更新日期：2011-07-01 00:00:00
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journal_title：Acta neuropathologica
pub_type： 杂志文章
doi：10.1007/BF00687332
更新日期：1984-01-01 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：1999-07-01 00:00:00
