title: Unraveling gene expression profiles in peripheral motor nerve from amyotrophic lateral sclerosis patients: insights into pathogenesis.
abstract: 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.
authors.affiliation: Experimental Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Nilo
authors.initials: N
authors.lastname: Riva
authors.affiliation: Laboratory of Genetics of Complex Neurological Disorders, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Clarelli
authors.affiliation: Experimental Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Teuta
authors.initials: T
authors.lastname: Domi
authors.affiliation: Experimental Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cerri
authors.affiliation: 2Neurology, IRCCS Istituto Clinico Humanitas, Milano University, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gallia
authors.affiliation: Axo-glia interactions Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: Trimarco
authors.affiliation: Laboratory of Genetics of Complex Neurological Disorders, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Brambilla
authors.affiliation: NEuroMuscular Omnicentre (NEMO), Niguarda Ca Granda Hospital, Milan, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Lunetta
authors.affiliation: Hand Surgery and Microsurgery Unit, IRCCS Humanitas Clinical Institute, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lazzerini
authors.affiliation: 3rd Neurology Unit, IRCCS Foundation "Carlo Besta" Neurological Institute, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lauria
authors.affiliation: Axo-glia interactions Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Taveggia
authors.affiliation: Department of Clinical Neurosciences, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Iannaccone
authors.affiliation: 2Neurology, IRCCS Istituto Clinico Humanitas, Milano University, Milan, Italy.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Nobile-Orazio
authors.affiliation: Experimental Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.|Universita` Vita e Salute San Raffaele, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Antonio
authors.affiliation: Laboratory of Genetics of Complex Neurological Disorders, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Martinelli-Boneschi
authors.affiliation: Experimental Neuropathology Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Quattrini
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D001706:Biopsy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000473:pathology*; D010525:Peripheral Nerves / Q000473:pathology*; D049490:Systems Biology; D059467:Transcriptome