Characterization of human sporadic ALS biomarkers in the familial ALS transgenic mSOD1g93a mouse model

Eitan Lilo, Shane Wald-Altman, Leonardo J. Solmesky, Keren Ben Yaakov, Noga Gershoni-Emek, Shlomo Bulvik, Ibrahim Kassis, Dimitrios Karussis, Eran Perlson, Miguel Weil*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 SOD1G93A 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 mSOD1G93A 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 mSOD1G93A mouse model and these biomarkers as molecular beacons to evaluate the effects of novel drugs/treatments in ALS.

Original languageEnglish
Article numberddt325
Pages (from-to)4720-4725
Number of pages6
JournalHuman Molecular Genetics
Volume22
Issue number23
DOIs
StatePublished - Dec 2013

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