| Autor: |
Basak I; Neurodegenerative and Lysosomal Disease Laboratory, Department of Biochemistry, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, 710 Cumberland Street, Dunedin, 9016, New Zealand., Wicky HE; Neurodegenerative and Lysosomal Disease Laboratory, Department of Biochemistry, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, 710 Cumberland Street, Dunedin, 9016, New Zealand., McDonald KO; Neurodegenerative and Lysosomal Disease Laboratory, Department of Biochemistry, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, 710 Cumberland Street, Dunedin, 9016, New Zealand., Xu JB; Neurodegenerative and Lysosomal Disease Laboratory, Department of Biochemistry, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, 710 Cumberland Street, Dunedin, 9016, New Zealand., Palmer JE; Neurodegenerative and Lysosomal Disease Laboratory, Department of Biochemistry, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, 710 Cumberland Street, Dunedin, 9016, New Zealand., Best HL; Neurodegenerative and Lysosomal Disease Laboratory, Department of Biochemistry, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, 710 Cumberland Street, Dunedin, 9016, New Zealand.; School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Wales, CF10 3AX, United Kingdom., Lefrancois S; Centre INRS-Institut Armand-Frappier, INRS, Laval, H7V 1B7, Canada.; Department of Anatomy and Cell Biology, McGill University, Montreal, H3A 2B2, Canada., Lee SY; Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA., Schoderboeck L; Neurodegenerative and Lysosomal Disease Laboratory, Department of Biochemistry, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, 710 Cumberland Street, Dunedin, 9016, New Zealand., Hughes SM; Neurodegenerative and Lysosomal Disease Laboratory, Department of Biochemistry, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, 710 Cumberland Street, Dunedin, 9016, New Zealand. stephanie.hughes@otago.ac.nz. |
| Abstrakt: |
Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is an incurable childhood brain disease. The thirteen forms of NCL are caused by mutations in thirteen CLN genes. Mutations in one CLN gene, CLN5, cause variant late-infantile NCL, with an age of onset between 4 and 7 years. The CLN5 protein is ubiquitously expressed in the majority of tissues studied and in the brain, CLN5 shows both neuronal and glial cell expression. Mutations in CLN5 are associated with the accumulation of autofluorescent storage material in lysosomes, the recycling units of the cell, in the brain and peripheral tissues. CLN5 resides in the lysosome and its function is still elusive. Initial studies suggested CLN5 was a transmembrane protein, which was later revealed to be processed into a soluble form. Multiple glycosylation sites have been reported, which may dictate its localisation and function. CLN5 interacts with several CLN proteins, and other lysosomal proteins, making it an important candidate to understand lysosomal biology. The existing knowledge on CLN5 biology stems from studies using several model organisms, including mice, sheep, cattle, dogs, social amoeba and cell cultures. Each model organism has its advantages and limitations, making it crucial to adopt a combinatorial approach, using both human cells and model organisms, to understand CLN5 pathologies and design drug therapies. In this comprehensive review, we have summarised and critiqued existing literature on CLN5 and have discussed the missing pieces of the puzzle that need to be addressed to develop an efficient therapy for CLN5 Batten disease. |
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