Galactosylceramidase Proteins (GALC)

Human Galactosylceramidase (GALC) interaction partners

1. The present study describes two GALC mutations shared by two Chinese siblings with juvenile-onset of Krabbe disease

2. rs17203398 associated with mucous membrane pemphigoid

3. The authors present the structure of a glycosphingolipid-processing complex, revealing how SapA and GALC form a heterotetramer with an open channel connecting the enzyme active site to the SapA hydrophobic cavity.

4. EMT phenotypes and GALC expression of CTCs are correlated with cancer metastasis and therapeutic outcomes, suggesting them to be potential markers for the prognosis of NSCLC.

5. Results show for the first time that during normal aging, psychosine metabolism is progressively dysfunctional, leading to its accumulation in the aging brain, especially in regions vulnerable to degeneration in Parkinson's disease (PD). These results underline the possibility that defects in the metabolism mediated by changes in GALC activity modify the risk of developing alpha-synuclein pathology in vulnerable patients.

6. we showed for the first time the specific alteration of beta-Galctosidase (Gal), beta-Galactosylcerebrosidase (GALC) in MCI patients. It is notable that in above peripheral biological samples the lysosomes are more sensitive to AD cellular metabolic alteration when compared to levels of Abeta-peptide or Tau proteins, similar in both AD groups analyzed

7. Enzyme activities (acid alpha-glucosidase (GAA), galactocerebrosidase (GALC), glucocerebrosidase (GBA), alpha-galactosidase A (GLA), alpha-iduronidase (IDUA) and sphingomyeline phosphodiesterase-1 (SMPD-1)) were measured on ~43,000 de-identified dried blood spot (DBS) punches, and screen positive samples were submitted for DNA sequencing to obtain genotype confirmation of disease risk

8. This review illustrated The Krabbe's disease is caused by mutation in the enzyme Beta-galactocerebrosidase.

9. This is the largest expression study of GALC variants/mutations found in Newborn screening and confirmed KD cases.

10. We demonstrated that a heterozygous GALC deletion does not play a significant role in the pathogenesis of normal tension glaucoma in a representative clinic-based population of South Koreans, unlike whites.

11. Mutations in GALC cause late-onset Krabbe disease with predominant cerebellar ataxia

12. promoter hypermethylation contributed to down-regulation of GALC Gene, implicating epigenetic inactivation of GALC may play a role in tumorigenesis of cancer.

13. Case Report: compound GALC heterozygosity in a boy with infantile Krabbe disease with severe clinical course.

14. GALC was downregulated by promoter hypermethylation and contributed to the pathogenesis of EBV-associated nasopharyngeal carcinoma

15. Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD.

16. Itis an exoglycosidase that catalyzes the hydrolysis of terminal beta-linked galactose residues and its deficiencies or mutation cause llysosomal diseases. (review)

17. Structural snapshots illustrate the catalytic cycle of beta-galactocerebrosidase, the defective enzyme in Krabbe disease.

18. Higher galactocerebrosidase activity is predictive of later symptom onset times but does not predict survival after symptom onset when controlling for the logarithm of age at onset.

19. study identified 4 novel mutations of the GALC gene in 2 unrelated Chinese families with Krabbe disease: one insertion mutation, c.1836_1837insT, one nonsense mutation, c.599C>A (p.S200X),one deletion mutation, c.1911 1_1911 5delGTAAG and one missense mutation, c.2041G>A

20. GALC mutation is associated with Krabbe disease.

Mouse (Murine) Galactosylceramidase (GALC) interaction partners

1. Data show that transgenic galactocerebrosidase (GALC) activity was mainly localized at the Purkinje cells layer in the cerebellum of the AAV-treated twitcher mice.

2. The results of this study indicated that the greater neurochemical pathology observed in the optic nerve than in the sciatic nerve of beta-gal -/- mice is likely due to the greater glycolipid storage in optic nerve.

3. This study demonistrated that galactosylceramidase Deficiency also casue neuromuscular dysfunction.

4. results show that GALCtwi-5J, a spontaneous mutation in murine GALC precisely matches the E130K missense mutation in patients with infantile Krabbe disease

5. Insights into the mechanisms underlying galactosylceramidase regulation of early post-natal neurogenic niches improve our understanding of the multi-component pathology of globoid cell leukodystrophy .

6. The crystal structures of GALC and the GALC-product complex, revealing a novel domain architecture with a previously uncharacterized lectin domain not observed in other hydrolases, are presented.

7. Data show that GALC and, possibly, other enzymes for the maintenance of niche functionality and health tightly control the concentration of these sphingolipids within HSPCs.

8. GALC is not restricted to myelinating cells but also to several neuronal cell types in the nervous system, such as hippocampal pyramidal neurons and cerebellar neurons.

9. Direct administration of these viral particles into the brains of neonatal mice with globoid cell leukodystrophy resulted in sustained expression of GALC activity, improved myelination

10. mutant oligodendrocytes can internalize exogenous galactocerebrosidase and maintain stable myelin, demonstrating that exogenous enzyme replacement will be a key strategy in the therapy of globoid cell leukodystrophy

11. Lentiviral vectors were designed and optimized for transfer of Galc expression in Twitcher brain.

12. Mouse model of globoid cell leukodystrophy contains a premature stop codon (W339X) in the galactosylceramidase (GALC) gene that abolishes enzymatic activity.

13. These results suggest that GALC deficiency not only affects myelinating glia but also leads to neuronal dysfunction. The contemporaneous neuropathology might help to explain the limited efficacy of current gene and cell therapies.