Functional omics approaches towards affected molecular pathways underlying various forms of Neuronal Ceroid Lipofuscinoses

This work illustrates a functional omic approach to a group of rare disease in childhood, the neuronal ceroid lipofucsinosis (NCL). We employed systematic approaches including functional proteomics, transcriptomic profiling, bioinformatics and cellular and murine disease models, in an effort to recognize molecular signatures and functional modules connected with over-expressed PPT1/NCL1 in infantile NCL, investigate the role at the lysosomal and mitochondrial levels of NCL5, a variant late-infantile form of NC and identify common molecular pathways and cross-talk among NCL proteins. By this study, we identified a potential role of PPT1 in modulating the function of membrane proteins related with neuronal excitability and epileptogenesis which can be associated with an altered gene dosage of wtCLN1, a cross-talk between CLN1 and CLN10 and a possible role of CLN5 in mitophagy, lipid homeostasis and gangliosides pathways Functional omic offers new information on disease pathogenesis, biomarkers and potential therapeutic targets in NCLs