Bioenergetic Profiling Applied to a Zebrafish Model of Neuronal Ceroid Lipofuscinosis, a Lysosomal Storage Disorder.

Abstract

Neuronal Ceroid Lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by autofluorescent lipopigment accumulation. NCLs consist of various types, spanning from CLN1 to CLN14 (except for "CLN9"), each linked to a particular mutated gene. Although the symptoms exhibit resemblances, the age at which each symptom manifests differs across the distinct types. Mitochondrial impairment has been implicated in the pathogenesis of NCLs, with studies suggesting contributions from dysfunctional oxidative phosphorylation and altered mitochondrial membrane potential to the progressive neurodegeneration observed in affected individuals. Utilizing Seahorse XF Analyzer, this study presents a method for the nuanced exploration of mitochondrial function and cellular metabolism, offering insights into potential therapeutic avenues. Zebrafish models reveal phenotypic similarities to human patients, making them promising for disease studies. Our research optimizes the Seahorse Mito Stress assay at 2 days post-fertilization (dpf) in zebrafish. This emerging approach holds great promise for identifying novel therapies.