title: Characterization of human sporadic ALS biomarkers in the familial ALS transgenic mSOD1(G93A) mouse model.
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder of motor neurons. Although most cases of ALS are sporadic (sALS) and of unknown etiology, there are also inherited familial ALS (fALS) cases that share a phenotype similar to sALS pathological and clinical phenotype. In this study, we have identified two new potential genetic ALS biomarkers in human bone marrow mesenchymal stem cells (hMSC) obtained from sALS patients, namely the TDP-43 (TAR DNA-binding protein 43) and SLPI (secretory leukocyte protease inhibitor). Together with the previously discovered ones-CyFIP2 and RbBP9, we investigated whether these four potential ALS biomarkers may be differentially expressed in tissues obtained from mutant SOD1(G93A) transgenic mice, a model that is relevant for at least 20% of the fALS cases. Quantitative real-time PCR analysis of brain, spinal cord and muscle tissues of the mSOD1(G93A) and controls at various time points during the progression of the neurological disease showed differential expression of the four identified biomarkers in correlation with (i) the tissue type, (ii) the stage of the disease and (iii) the gender of the animals, creating thus a novel spatiotemporal molecular signature of ALS. The biomarkers detected in the fALS animal model were homologous to those that were identified in hMSC of our sALS cases. These results support the possibility of a molecular link between sALS and fALS and may indicate common pathogenetic mechanisms involved in both types of ALS. Moreover, these results may pave the path for using the mSOD1(G93A) mouse model and these biomarkers as molecular beacons to evaluate the effects of novel drugs/treatments in ALS.
authors.affiliation: Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences and.
authors.forename: Eitan
authors.initials: E
authors.lastname: Lilo
authors.forename: Shane
authors.initials: S
authors.lastname: Wald-Altman
authors.forename: Leonardo J
authors.initials: LJ
authors.lastname: Solmesky
authors.forename: Keren
authors.initials: K
authors.lastname: Ben Yaakov
authors.forename: Noga
authors.initials: N
authors.lastname: Gershoni-Emek
authors.forename: Shlomo
authors.initials: S
authors.lastname: Bulvik
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Kassis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karussis
authors.forename: Eran
authors.initials: E
authors.lastname: Perlson
authors.forename: Miguel
authors.initials: M
authors.lastname: Weil
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000235:genetics* / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult; D000099156:Superoxide Dismutase 2
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D053481:Secretory Leukocyte Peptidase Inhibitor; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2