Lopez, Grisel (NHGRI)
Stubblefield, Barbara (NHGRI)
This technology includes six cell lines for the study of Glucocerebrosidase (GBA1) mutations which could be used for the evaluation and eventual treatments for conditions such as Gaucher's disease and Parkinson's disease. GBA1 is a lysosomal enzyme, responsible for breakdown of a fatty material called glucocerebroside (or glucosyl ceramide). Deficiency or malfunction of GBA1 leads to the accumulation of insoluble glucocerebrosides (derived mostly from ingested red and white blood cell membranes) in tissues, which is a major symptom of Gaucher disease. Gaucher disease is a rare and heterogeneous disorder, caused by inherited GBA1 genetic mutations. The disease has been classified into three types, two of which include neurological abnormalities. There also appears to be a link between GBA1 mutations, Gaucher's disease and Parkinson's disease, thus, the insights gained from studying Gaucher's disease could allow for better understanding of other neurodegenerative disorders.
These cell lines can be used to study the defects in GBA1 gene and protein and to screen small molecules for involvement in Gaucher disease and other neurodegenerative diseases involving GBA1.
The GBA1 N370S mutation is involved in non-neuronopathic type of Gaucher disease, thus the homozygous line can likely serve as a good control line for studying Parkinson’s disease and neurodegenerative disorders that involve other GBA1 mutations.