Satisfactory Essays
Krabbe's disease is an inherited neurological disease caused by galactosylceramidase deficiency in children. Castelvetri et al. focused on psychosine in this study as a potential causative agent in Krabbe disease because psychosine (galactosylsphingosine) has shown to be a causative agent of the pathological condition found in the nervous system of patients with Krabbe’s disease. They supported the role of psychosine as a potential causative agent in Krabee disorder by discussing the important role, which psychosine play in this disease. Castelvetri et al. stated that the accumulation of psychosine is recognized to be a causative lipid for the loss of oligodendrocytes and myelin sheath in Krabbe's disease. Thus, psychosine is highly cytotoxic and responsible for the extensive pathology of the disease. Moreover, it has been shown that psychosine is responsible for loss in function in galactosylceramidase lysosomal activity that results in demyelination and vulnerability of different neurons. Additionally, by examining the in vitro myelin free, it showed that psychosine was able to inhibit fast axonal transport (FAT) via activating axonal PP1 and GSK3β in the axon. Defects in FAT are indicated by the formation of localized swelling of the axon. Castelvetri et al. showed that FAT defects present in cellular and animal models of Krabbe disease and sphingolipid psychosine has been demonstarated as FAT inhibitor. Thus, psychosine is highly cytotoxic and responsible for the extensive pathology of the disease that is able to block fast axonal transport. Additionally, this is the first study to show the molecular mechanism of dying back degeneration in this inherited genetic disease.

To examine whether sphingolipid psychosine is able to i...

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...n et al. 2012).
Castelvetri et al. indicated that due to the interference of different pathogenic mechanisms with each other, it affect the efficiency of hematogenous replacement therapy. Additionally, their results showed that use of psychosine as a FAT inhibitor was able to activate the PP1-GSK3β pathway, which could be used as a potential therapy for Krabbe disease neurodegeneration by reversing FAT defects. Interestingly, they declared that the pharmacological treatment that they used in their study was not associated with any metabolic correction. Therefore, the treated mutants in their research were able to demonstrate neurological symptoms of the disease. For all these reasons, they concluded that neuroprotective treatments could be used with the traditional hematogenous replacement as a potential therapy for Krabbe disease as well as other leukodystrophies.
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