期刊
NEUROBIOLOGY OF DISEASE
卷 100, 期 -, 页码 62-74出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2017.01.001
关键词
Batten disease; Neuronal ceroid lipofuscinosis; CLN5; CLN6; Neuronal cell culture; Gene therapy; Autophagy
资金
- New Zealand Neurological Foundation
- Otago School of Medical Sciences Dean's Bequest Funds
- Brain Health Research Centre, NZ
- University of Otago Doctoral Scholarship
- Hanns Mohler Roche scholarship
- NN by a Neurological Foundation Miller Scholarship
- Brain Research New Zealand Centre of Research Excellence
Batten disease (neuronal ceroid lipofuscinosis) refers to a group of neurodegenerative lysosomal storage diseases predominantly affecting children. There are currently no effective treatments, and the functions of many of the associated gene products are unknown. Here we characterise fetal neural cultures from two genetically distinct sheep forms of Batten disease, with mutations in the lysosomal protein encoding gene CLN5 and endoplasmic reticulum membrane protein encoding gene CLN6, respectively. We found similar reductions in autophagy, acidic organelles and synaptic recycling in both forms compared to unaffected cells. We then developed a high throughput screen and tested for correction of deficient cells with lentiviral-mediated CLN5 or CLN6 gene transfer and fibrate drugs, gemfibrozil and fenofibrate in CLN6 deficient neural cultures. These assays provide a simple system to rapidly screen candidate therapies or libraries of drugs prior to in vivo testing. (C) 2017 Elsevier Inc. All rights reserved.
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