Galectin-3 is a candidate biomarker for amyotrophic lateral sclerosis: discovery by a proteomics approach.
The discovery of biomarkers for neurodegenerative diseases will have a major impact on the efficiency of therapeutic clinical trials and may be important for understanding basic pathogenic mechanisms. We have approached the discovery of protein biomarkers for amyotrophic lateral sclerosis (ALS) by profiling affected tissues in a relevant animal model and then validating the findings in human tissues. Ventral roots from SOD1(G93A) "ALS" mice were analyzed by label-free quantitative mass spectrometry, and the resulting data were compared with data for matched samples from nontransgenic littermates and transgenic mice carrying wild-type human SOD1 (SOD1(WT)). Of 1299 proteins, statistical inference of the data in the three groups identified 14 proteins that were dramatically altered in the ALS mice compared with the two control groups. The protein galectin-3 emerged as a lead biomarker candidate on the basis of its differential expression as assessed by immunoblot and immunocytochemistry in SOD1(G93A) mice as compared to controls and because it is a secreted protein that could potentially be measured in human biofluids. Spinal cord tissue from ALS patients also exhibited increased levels of galectin-3 when compared to controls. Further measurement of galectin-3 in cerebrospinal fluid samples showed that ALS patients had approximately twice as much galectin-3 as normal and disease controls. These results provide the proof of principle that biomarker identification in relevant and well-controlled animal models can be translated to human disease. The challenge is to validate our biomarker candidate proteins as true biomarkers for ALS that will be useful for diagnosis and/or monitoring disease activity in future clinical trials.
Zhou
Jian-Ying
JY
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Afjehi-Sadat
Leila
L
Asress
Seneshaw
S
Duong
Duc M
DM
Cudkowicz
Merit
M
Glass
Jonathan D
JD
Peng
Junmin
J
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015415:Biomarkers / Q000032:analysis* / Q000134:cerebrospinal fluid; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D037502:Galectin 3 / Q000032:analysis* / Q000134:cerebrospinal fluid; D006801:Humans; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D040901:Proteomics / Q000379:methods*; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D037502:Galectin 3; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase