TY - JOUR
T1 - CLN5 deficiency impairs glucose uptake in Batten disease.
AU - Marchese, Maria
AU - Bernardi, Sara
AU - Vivarelli, Rachele
AU - Doccini, Stefano
AU - Santucci, Lorenzo
AU - Ogi, Asahi
AU - Licitra, Rosario
AU - Zang, Jingjing
AU - Soliymani, Rabah
AU - Mero, Serena
AU - Neuhauss, Stefan CF
AU - Signore, Giovanni
AU - Lalowski, Maciej
AU - Santorelli, Filippo Maria
PY - 2025/1/2
Y1 - 2025/1/2
N2 - CLN5 disease, a form of juvenile dementia within the neuronal ceroid lipofuscinosis (NCL), is associated with mutations in the CLN5 gene encoding the lysosomal bis(monoacylglycero)phosphate (BMP) synthase, essential for BMP production and lysosomal function. Limited knowledge of cellular mechanisms and unclear drug targets hinder translating this to children's treatment, which remains symptomatic. We developed and characterized a new cln5 knock-out zebrafish model that replicates key features and molecular signatures of the human disease. Loss of Cln5 function in vivo altered axonal growth of retinal ON-bipolar cells revealing new disease features. Additionally, multi-omic analyzes at different developmental stages, revealed an impaired glucose metabolism as an original finding in NCL. This work demonstrates the profound metabolic impact of CLN5 dysfunction, offering a promising avenue toward targeted therapies for juvenile dementia.
AB - CLN5 disease, a form of juvenile dementia within the neuronal ceroid lipofuscinosis (NCL), is associated with mutations in the CLN5 gene encoding the lysosomal bis(monoacylglycero)phosphate (BMP) synthase, essential for BMP production and lysosomal function. Limited knowledge of cellular mechanisms and unclear drug targets hinder translating this to children's treatment, which remains symptomatic. We developed and characterized a new cln5 knock-out zebrafish model that replicates key features and molecular signatures of the human disease. Loss of Cln5 function in vivo altered axonal growth of retinal ON-bipolar cells revealing new disease features. Additionally, multi-omic analyzes at different developmental stages, revealed an impaired glucose metabolism as an original finding in NCL. This work demonstrates the profound metabolic impact of CLN5 dysfunction, offering a promising avenue toward targeted therapies for juvenile dementia.
U2 - 10.1101/2025.01.02.630719
DO - 10.1101/2025.01.02.630719
M3 - Article
VL - 2025.01.02
JO - bioRxiv : the preprint server for biology
JF - bioRxiv : the preprint server for biology
IS - 630719
ER -