Proteomic analysis of mucopolysaccharidosis IIIB mouse brain

Mucopolysaccharidosis IIIB (MPS IIIB) is an inherited metabolic disease due to deficiency of α-N-Acetylglucosaminidase (NAGLU) enzyme with subsequent storage of undegradedheparan sulfate (HS). The main clinical manifestations of the disease are profound intellectual disability and neurodegeneration. To identify potential biomarkers and novel neuropathological mechanisms of MPS IIIB, a label-free quantitative proteomic approach was applied to compare the proteome profile of brains from MPS IIIB and control mice. Proteins were identified through a bottom up analysis and 130 were significantly under-represented and 74 over-represented in MPS IIIB mouse brains compared to wild type (WT). Multiple bioinformatic analyses of the differentially abundant proteins allowed to define three major clusters: proteins involved in cytoskeletal regulation, synaptic vesicle trafficking, and energy metabolism. The results highlight the involvement of these clustered proteins in the neuropathology of MPS IIIB disease. The proteins identified in this study would provide potential targets for diagnostic and therapeutic studies of MPS IIIB.