An altered secretome is an early marker of the pathogenesis of CLN6 Batten disease

Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited childhood neurodegenerative disorders. In addition to the accumulation auto-fluorescent storage material in lysosomes, NCLs largely characterised by region-specific neuroinflammation that can predict neuron loss. These phenotypes suggest alterations extracellular environment—making secretome an area significant interest. This study investigated CLN6 (ceroid-lipofuscinosis neuronal protein 6) variant NCL. To investigate secretome, we co-cultured neurons and glia isolated from Cln6nclf or Cln6± mice, utilised mass spectrometry compare constituents conditioned media. The changes noted cathepsin enzymes, were further via western blotting enzyme activity assays. Viral-mediated gene therapy was used try rescue wild-type phenotype restore secretome—both vitro co-cultures vivo mouse plasma. cells, proteomics revealed marked increase catabolic cytoskeletal-associated proteins—revealing new similarities between pathogenic signatures with other were, part, corrected intervention, suggesting these proteins as candidate biomarkers. Importantly, show promise for translation, Cathepsin L (CTSL) reduced both plasma samples post gene-therapy. work suggests plays role pathogenesis highlights its potential use model. Proteomic present list biomarkers monitoring disease assessing therapeutics future studies.