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La sclerosi laterale amiotrofica è una malattia neurodegenerativa caratterizzata da una paralisi muscolare progressiva dovuta a una degenerazione dei motoneuroni. In un articolo pubblicato su Human Molecular Genetics di agosto l’equipe della dr.ssa Lili Kudo ha confrontato i sintomi di tale patologia presenti nei topi con quelli degli uomini. Tale studio ha permesso di identificare una serie di nuovi marcatori precoci della SLA (CNGA3, CRB1, OTUB2, MMP14, SLK, DDX58, RSPO2) dei quali alcuni potrebbero essere dei marcatori sanguigni (Nefh, Prph, e Mgll).

Nel seguito l’abstract dello studio.

Integrative gene–tissue microarray-based approach for identification of human disease biomarkers: application to amyotrophic lateral sclerosis 

Lili C. Kudo, Liubov Parfenova, Nancy Vi, Kimbley Lau, Justine Pomakian, Paul Valdmanis, Guy A. Rouleau, Harry V. Vinters, Martina Wiedau-Pazos, and Stanislav L. Karsten.
+ Author Affiliations
Department of Neurology and Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA,
NeuroInDx, Inc., 1655 East 28th Street, Signal Hill, CA 90755, USA,
Division of Neuroscience, Department of Neurology, Los Angeles Biomedical Research Institute and
Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, CA 90502, USA and Center for the Study of Brain Diseases, Notre-Dame Hospital, Centre de Recherche du CHUM, University of Montreal, Montreal, QC, Canada H2L4M1
*To whom correspondence should be addressed at: Division of Neuroscience, Hanley-Hardison Research Center, Los Angeles Biomedical Research Institute, Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA 90502, USA. Tel: +1 3107811477; Email:
Received May 7, 2010.
Accepted June 3, 2010. 


Advances in genomics and proteomics permit rapid identification of disease-relevant genes and proteins. Challenges include biological differences between animal models and human diseases, high discordance between DNA and protein expression data and a lack of experimental models to study human complex diseases. To overcome some of these limitations, we developed an integrative approach using animal models, postmortem human material and a combination of high-throughput microarray methods to identify novel molecular markers of amyotrophic lateral sclerosis (ALS). We used laser capture microdissection coupled with microarrays to identify early transcriptome changes occurring in spinal cord motor neurons or surrounding glial cells. Two models of familial motor neuron disease, SOD1G93A and TAUP301L, transgenic mice were used at the presymptomatic stage. Identified gene expression changes were predominantly model-specific. However, several genes were regulated in both models. The relevance of identified genes as clinical biomarkers was tested in the peripheral blood transcriptome of presymptomatic SOD1G93A animals using custom-designed ALS microarray. To confirm the relevance of identified genes in human sporadic ALS (SALS), selected corresponding protein products were examined by high-throughput immunoassays using tissue microarrays constructed from human postmortem spinal cord tissues. Genes that were identified by these experiments and located within a linkage region associated with familial ALS/frontotemporal dementia were sequenced in several families. This large-scale gene and protein expression study pointing to distinct molecular mechanisms of TAU- and SOD1-induced motor neuron degeneration identified several new SALS-relevant proteins (CNGA3, CRB1, OTUB2, MMP14, SLK, DDX58, RSPO2) and putative blood biomarkers, including Nefh, Prph and Mgll.

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