Glycosphingolipidoses: Beyond the enzymatic defect

@article{RaasRothschild2004GlycosphingolipidosesBT,
  title={Glycosphingolipidoses: Beyond the enzymatic defect},
  author={Annick Raas-Rothschild and Irene Pankova-Kholmyansky and Yaacov Kacher and Anthony H. Futerman},
  journal={Glycoconjugate Journal},
  year={2004},
  volume={21},
  pages={295-304}
}
The glycosphingolipid lysosomal storage diseases are a group of monogenic human disorders caused by the impaired catalytic activity of enzymes responsible for glycosphingolipid catabolism. Clinical presentation of the diseases is heterogeneous, with little obvious correlation between the kind of accumulating glycosphingolipid and disease progression or pathogenesis. In this review, we discuss clinical symptoms of this group of diseases, and attempt to link disease progression and pathology with… 
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  • 2010
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References

SHOWING 1-10 OF 51 REFERENCES
The pathogenesis of glycosphingolipid storage disorders.
Lysosomal Storage Diseases: Is Impaired Apoptosis a Pathogenic Mechanism?
TLDR
The potential role of apoptotic cell death in the development of the cellular and tissue lesions seen in lysosomal storage disorders, and particularly in neurological diseases, is discussed and a list of observations documenting either a decrease or an exacerbation in apoptosis induction are presented.
Insights into the diagnosis and treatment of lysosomal storage diseases.
TLDR
Diagnosis of suspected patients can usually be made by measuring the activity of an enzyme or concentration of a metabolite in easily obtained tissue samples, and the considerable diagnostic experience of the laboratory aid the physician in selecting the appropriate tests to perform.
The cell biology of lysosomal storage disorders
TLDR
The biochemistry of lysosomal storage disorders is summarized and downstream cellular pathways that are potentially affected in these disorders are discussed and that might help to delineate their pathological mechanisms.
Secondary accumulation of gangliosides in lysosomal storage disorders.
  • S. Walkley
  • Biology, Chemistry
    Seminars in cell & developmental biology
  • 2004
[Niemann-Pick disease types A and B].
  • K. Ohno
  • Biology, Chemistry
    Nihon rinsho. Japanese journal of clinical medicine
  • 1995
TLDR
Progress suggest that ceramide, which is produced by sphingomyelinase from sphingomelin, is an important factor for signal transduction of cell differentiation and abnormal phospholipid signaling is involved in the pathogenesis of neuronal cell dysfunction of Niemann-Pick disease type A.
Molecular pathophysiology in Tay-Sachs and Sandhoff diseases as revealed by gene expression profiling.
TLDR
Examination of genes that showed altered expression in both patients revealed molecular details of the pathophysiology of the disorders relating to neuronal dysfunction and loss, consistent with a model of neurodegeneration that includes inflammation as a factor leading to the precipitous loss of neurons in individuals with these disorders.
Glycosphingolipids and cell death
TLDR
This review summarizes current knowledge of the involvement of glycosphingolipids in cell death and in other pathological processes and diseases.
5 Neuronopathic forms of Gaucher's disease
...
1
2
3
4
5
...