In a new study conducted by Shin et al., it was reported that the gene defect underlying Krabbe disease causes degeneration of neurons directly, independent of its effects on other cell types. The study suggested that neurons may be affected independently, however, the hypothesis was difficult to test, as galactosylceramidase (GALC) is expressed ubiquitously in the brain, and its disease-related loss occurs in all cell types. GALC is an enzyme that is active in the lysosomes, and its absence leads to the build-up of the lipid psychosine. 

During an experimental study in a mouse model, there was no loss of oligodendrocytes, but lack of neuronal GALC expression did lead to a reduction in myelination, presumably through toxic effects on myelin sheaths from the accumulated psychosine. The results indicated that neuronal expression of galactosyl ceramidase is essential to maintain and protect neuronal function, independent of its effects on myelin-producing oligodendrocytes. The research team concluded that a lack of the enzyme in neurons may contribute directly to the pathogenesis of Krabbe disease and that therapies for the disease may need to address the absence of neuronal expression of galactosyl ceramidase in order to be fully effective. 

Mr. Shin added that "Our study is the first attempt in a preclinical live animal model to directly investigate the neuronal role of the Krabbe disease gene galactosyl ceramides”. On generating a neuron-specific mutant of Krabbe disease in a live mouse model, the researchers found an intrinsic neuronal role for the GALC enzyme, suggesting that neuronal galactosyl ceramidase has a primary role in neuronal homeostasis. Thus, galactosyl ceramidase-depleted neurons can cause Krabbe disease.

(Source: https://www.hindustantimes.com/lifestyle/health/krabbe-disease-causes-degeneration-of-neurons-directly-study-101657087387988.html )