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J Proteome Res. 2017 Oct 6;16(10):3787-3804. doi: 10.1021/acs.jproteome.7b00460. Epub 2017 Aug 28.

Proteomic Analysis of Brain and Cerebrospinal Fluid from the Three Major Forms of Neuronal Ceroid Lipofuscinosis Reveals Potential Biomarkers.

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Center for Advanced Biotechnology and Medicine , Piscataway, New Jersey 08854, United States.
Department of Biochemistry and Molecular Biology, Robert-Wood Johnson Medical School, Rutgers Biomedical Health Sciences , Piscataway, New Jersey 08854, United States.
Neurogenetics DNA Diagnostic Laboratory, Department of Neurology, Massachusetts General Hospital, Harvard Medical School , Boston, Massachusetts 02115, United States.
Department of Biostatistics, School of Public Health, Rutgers - The State University of New Jersey , Piscataway, New Jersey 08854, United States.


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 long-term 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.


autopsy; brain; cerebrospinal fluid; lysosome; neuronal ceroid lipofuscinosis; proteomic

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