Unraveling gene expression profiles in peripheral motor nerve from amyotrophic lateral sclerosis patients: Insights into pathogenesis

Nilo Riva, Ferdinando Clarelli, T. Domi, Federica Cerri, Francesca Gallia, Amelia Trimarco, Paola Brambilla, Christian Lunetta, Alberto Lazzerini, Giuseppe Lauria, Carla Taveggia, Sandro Iannaccone, Eduardo Nobile-Orazio, Giancarlo Comi, Maurizio D'Antonio, Filippo Martinelli Boneschi, Angelo Quattrini

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The aim of the present study is to investigate the molecular pathways underlying amyotrophic lateral sclerosis (ALS) pathogenesis within the peripheral nervous system. We analyzed gene expression changes in human motor nerve diagnostic biopsies obtained from eight ALS patients and seven patients affected by motor neuropathy as controls. An integrated transcriptomics and system biology approach was employed. We identified alterations in the expression of 815 genes, with 529 up-regulated and 286 down-regulated in ALS patients. Up-regulated genes clustered around biological process involving RNA processing and protein metabolisms. We observed a significant enrichment of up-regulated small nucleolar RNA transcripts (p = 2.68∗10-11) and genes related to endoplasmic reticulum unfolded protein response and chaperone activity. We found a significant down-regulation in ALS of genes related to the glutamate metabolism. Interestingly, a network analysis highlighted HDAC2, belonging to the histone deacetylase family, as the most interacting node. While so far gene expression studies in human ALS have been performed in postmortem tissues, here specimens were obtained from biopsy at an early phase of the disease, making these results new in the field of ALS research and therefore appealing for gene discovery studies.

Original languageEnglish
Article number39297
JournalScientific Reports
Publication statusPublished - Dec 16 2016


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