Proteomics analysis of the brain from a Gaucher disease mouse identifies pathological pathways including a possible role for transglutaminase 1

Gaucher disease (GD) is a lysosomal storage disorder (LSD) caused by the defective activity of acid β-glucosidase (GCase;GBA1 gene). Neurological forms of GD (nGD) can be generated in mice by intra-peritoneal injection of conduritol B-epoxide (CBE) which irreversibly inhibits GCase. We performed non-targeted proteomics on brains from mice injected with 50  mg/kg body weight CBE. Approximately 5000 detected proteins were analyzed and compared with RNAseq data from previous studies. One protein, transglutaminase 1 (TGM1), was absent from the control group but was found at high levels in CBE-injected mice, and located in the extracellular matrix in th e cortex but intracellularly in the cerebellum. Together, the proteomics data confirm previous data and add additional mechanistic understanding about nGD pathology. The figure was generated using BioRender.com AbstractGaucher disease (GD) is a lysosomal storage disorder (LSD) caused by the defective activity of acid β-glucosidase (GCase) which results from mutations inGBA1. Neurological forms of GD (nGD) can be generated in mice by intra-peritoneal injection of conduritol B-epoxide (CBE) which irreversibly inhibits GCase. Using this approach, a number of pathological pathways have been identified in mouse brain by RNAseq. However, unlike transcriptomics, proteomics gives direct information about protein expression which is more likely to provide insight into which cellular pathways are impacted in disease. We now perform non-t...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research