Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a neurodegenerative disorder caused by defective function of the lysosomal membrane glycoprotein CLN3. The activity of the lysosomal acid phosphatase (LAP/ACP2) was found to be significantly increased in the cerebellum and brain stem of Cln3-targeted mice during the early stages of postnatal life. Histochemical localization studies revealed an increased LAP/ACP2 staining intensity in neurons of the cerebral cortex of 48-week-old Cln3-targeted mice as compared with controls. Additionally, the expression of another lysosomal membrane protein LAMP-2 was increased in all brain areas. Knockdown of CLN3 expression in HeLa cells by RNA interference also resulted in increased LAP/ACP2 and LAMP-2 expression. Finally in fibroblasts of two juvenile neuronal ceroid lipofuscinosis patients elevated levels of LAP/ACP2 were found. Both activation of gene transcription and increased protein half-life appear to contribute to increased LAP/ACP2 protein expression in CLN3-deficient cells. The data suggest that lysosomal dysfunction and accumulation of storage material require increased biogenesis of LAP/ACP2 and LAMP-2 positive membranes which makes LAP/ACP2 suitable as biomarker of Batten disease.

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doi.org/10.1111/j.1471-4159.2007.04920.x, hdl.handle.net/1765/35091
Journal of Neurochemistry
Erasmus MC: University Medical Center Rotterdam

Pohl, S., Mitchison, H., Kohlschütter, A., Braulke, T., Storch, S., & van Diggelen, O. (2007). Increased expression of lysosomal acid phosphatase in CLN3-defective cells and mouse brain tissue. Journal of Neurochemistry, 103(6), 2177–2188. doi:10.1111/j.1471-4159.2007.04920.x