Increased Zinc and Manganese in Parallel with Neurodegeneration, Synaptic Protein Changes and Activation of Akt/GSK3 Signaling in Ovine CLN6 Neuronal Ceroid Lipofuscinosis
Katja M Kanninen, Alexandra Grubman, Jodi Meyerowitz, Clare Duncan, Jiang-Li Tan, Sarah J Parker, Peter J Crouch, Brett M Paterson, James L Hickey, Paul S Donnelly, Irene Volitakis, Imke Tammen, David N Palmer, Anthony R White
PLOS ONE | PUBLIC LIBRARY SCIENCE | Published : 2013
Mutations in the CLN6 gene cause a variant late infantile form of neuronal ceroid lipofuscinosis (NCL; Batten disease). CLN6 loss leads to disease clinically characterized by vision impairment, motor and cognitive dysfunction, and seizures. Accumulating evidence suggests that alterations in metal homeostasis and cellular signaling pathways are implicated in several neurodegenerative and developmental disorders, yet little is known about their role in the NCLs. To explore the disease mechanisms of CLN6 NCL, metal concentrations and expression of proteins implicated in cellular signaling pathways were assessed in brain tissue from South Hampshire and Merino CLN6 sheep. Analyses revealed increa..View full abstract
KMK was supported by the Sigrid Juselius Foundation, the Academy of Finland, the Paulo Foundation and the Maud Kuistila Memorial Foundation. ARW was supported by an Australian Research Council ARC Future Fellowship. This work was supported by funding from the National Health and Medical Research Council of Australia. The work at Lincoln University was supported in part by the Neurological Foundation of New Zealand and the Batten Disease Support and Research Association. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.