PLoS ONENeurosciencePeer-reviewed journal article
Progranulin deficiency leads to reduced glucocerebrosidase activity
Xiaolai ZhouiD, Daniel H. Paushter, Mitchell D. Pagan, Dong-Sung KimiD, Mariela Nunez Santos, Raquel L. LiebermaniD, Herman S. OverkleeftiD, Ying SuniD, Marcus Bustamante SmolkaiD, Fenghua HuiD
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Abstract
Mutation in the GRN gene, encoding the progranulin (PGRN) protein, shows a dose-dependent disease correlation, wherein haploinsufficiency results in frontotemporal lobar degeneration (FTLD) and complete loss results in neuronal ceroid lipofuscinosis (NCL). Although the exact function of PGRN is unknown, it has been increasingly implicated in lysosomal physiology. Here we report that PGRN interacts with the lysosomal enzyme, glucocerebrosidase (GBA), and is essential for proper GBA activity. GBA activity is significantly reduced in tissue lysates from PGRN-deficient mice. This is further evidence that reduced lysosomal hydrolase activity may be a pathological mechanism in cases of GRN-related FTLD and NCL.
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