A new study found that the gene defect which causes the Krabbe disease can harm brain cells directly. Moreover, this effect is independent of what the genes could do in other cell types.
According to the findings, there is significant data that scientists could gather regarding the mechanism of action in mutant genes. The results from the investigation could also contribute to future studies about the disease process for developing improved and effective therapy solutions. Specialists led the research from the University of Buffalo.
Krabbe Disease and Gene Mutation
Krabbe disease is a rare autosomal recessive neurodegenerative condition commonly due to a particular mutation in a gene called galactosylceramide or GALC.
GALC is an enzyme that is responsible for controlling lipid psychosis. It is found active in lysosomes. When GALC is absent, the lipid lysosomes build up excessively. They could result in the degeneration and destabilization of the brain organ and the cell deaths of the neurons.
The main pathological symptom of Krabbe disease is the lack of myelin insulation throughout the nerves. The cause that triggers the disease process was long-believed as the oligodendrocytes, cells that provide the myelin to and give the majority of support needed by brain cells. Hence, the lower production of myelin is linked to the degeneration of neurons.
Recent theories suggest that neurons might have been affected by other factors, specifically by their properties found right in each of them. GALC has been suspected as the trigger of degeneration, but the challenging steps of examining the gene inside the brain cells and its general impacts on other cell types required multiple studies.
The latest study utilized a mouse model with their GALC genes only turned off in their neurons. Observations revealed that psychosine accumulated in the brain cells, leading to the lysosomes incurring abnormal shapes, swollen axons, and, as expected, high rates of neuronal death.
Cell Death Caused by Absence of Gene in Neurons
The cell death in neurons affected the brain functions of the model in terms of coordination and motor ability. There was also neuroinflammation recorded from the brain. The authors noted no significant loss of oligodendrocytes, but the absence of GALC expression led to the decline of myelination, EurekAlert reports.
University at Buffalo's Institute for Myelin and Glia Exploration specialist Daesung Shin, who also authored the study, explained that the results are the first time that a certain neuronal expression was proved essential to protect and keep the state of brain cell functions, independent of the effects by the myelin-producing oligodendrocytes.
It was clear that the lack of enzymes in the brain cells has directly induced the pathogenesis in Krabbe disease, and future research for the development of solutions against the condition should consider the absence of this neuronal expression for the therapy to be more effective, Shin continued.
The study was published in the journal PLOS Biology, titled "Neuron-specific ablation of the Krabbe disease gene galactosylceramidase in mice results in neurodegeneration."
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