期刊
JOURNAL OF PROTEOME RESEARCH
卷 16, 期 10, 页码 3787-3804出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.7b00460
关键词
neuronal ceroid lipofuscinosis; lysosome; autopsy; brain; cerebrospinal fluid; proteomic
资金
- NINDS/NIMH
- National Multiple Sclerosis Society
- Department of Veterans Affairs
- NIH [P30NS046593, S10RR024584, R01NS37918, R21NS088786, P30CA072720]
Clinical trials have been conducted for the neuronal ceroid lipofuscinoses (NCLs), a group of neurodegenerative lysosomal diseases that primarily affect children. Whereas clinical rating systems will evaluate longterm efficacy, biomarkers to measure short-term response to treatment would be extremely valuable. To identify candidate biomarkers, we analyzed autopsy brain and matching CSF samples from controls and three genetically distinct NCLs due to deficiencies in palmitoyl protein thioesterase 1 (CLN1 disease), tripeptidyl peptidase 1 (CLN2 disease), and CLN3 protein (CLN3 disease). Proteomic and biochemical methods were used to analyze lysosomal proteins, and, in general, we find that changes in protein expression compared with control were most similar between CLN2 disease and CLN3 disease. This is consistent with previous observations of biochemical similarities between these diseases. We also conducted unbiased proteomic analyses of CSF and brain using isobaric labeling/quantitative mass spectrometry. Significant alterations in protein expression were identified in each NCL, including reduced STXBP1 in CLN1 disease brain. Given the confounding variable of post-mortem changes, additional validation is required, but this study provides a useful starting set of candidate NCL biomarkers for further evaluation.
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