The homozygous sheep were found to have significantly reduced PPT1 enzyme activity and accumulate autofluorescent storage material, as is observed in CLN1 patients.
Moreover, these modules were interrelated with the pathological effects associated with loss of PPT1 function, similarly as observed in the <i>Ppt1</i> knockout mice and patients with CLN1 disease.
To examine the effects of PPT1 deficiency on several well-defined neuronal signaling and cell death pathways, different toxic insults were applied in cerebellar granule neuron cultures prepared from wild type (WT) and palmitoyl protein thioesterase 1-deficient (Ppt1 <sup>-/-</sup> ) mice, a model of infantile CLN1 disease.
To identify candidate biomarkers, we analyzed autopsy brain and matching CSF samples from controls and three genetically distinct NCLs due to deficiencies in palmitoyl protein thioesterase 1 (CLN1 disease), tripeptidyl peptidase 1 (CLN2 disease), and CLN3 protein (CLN3 disease).
Infantile neuronal ceroid lipofuscinosis (INCL, or CLN1 disease) is an inherited neurodegenerative storage disorder caused by a deficiency of the lysosomal enzyme palmitoyl protein thioesterase 1 (PPT1).
We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced.
Infantile neuronal ceroid lipofuscinosis (INCL, infantile Batten disease, or infantile CLN1 disease) is caused by a deficiency in the soluble lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1) and has the earliest onset and fastest progression of all the NCLs.