title: Expression of microRNAs in human post-mortem amyotrophic lateral sclerosis spinal cords provides insight into disease mechanisms.
abstract: Amyotrophic lateral sclerosis is a late-onset and terminal neurodegenerative disease. The majority of cases are sporadic with unknown causes and only a small number of cases are genetically linked. Recent evidence suggests that post-transcriptional regulation and epigenetic mechanisms, such as microRNAs, underlie the onset and progression of neurodegenerative disorders; therefore, altered microRNA expression may result in the dysregulation of key genes and biological pathways that contribute to the development of sporadic amyotrophic lateral sclerosis. Using systems biology analyses on postmortem human spinal cord tissue, we identified dysregulated mature microRNAs and their potential targets previously implicated in functional process and pathways associated with the pathogenesis of ALS. Furthermore, we report a global reduction of mature microRNAs, alterations in microRNA processing, and support for a role of the nucleotide binding protein, TAR DNA binding protein 43, in regulating sporadic amyotrophic lateral sclerosis-associated microRNAs, thereby offering a potential underlying mechanism for sporadic amyotrophic lateral sclerosis.
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI 48109 USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Figueroa-Romero
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI 48109 USA.
authors.forename: Junguk
authors.initials: J
authors.lastname: Hur
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI 48109 USA.
authors.forename: J Simon
authors.initials: JS
authors.lastname: Lunn
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI 48109 USA.
authors.forename: Ximena
authors.initials: X
authors.lastname: Paez-Colasante
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI 48109 USA.
authors.forename: Diane E
authors.initials: DE
authors.lastname: Bender
authors.affiliation: Division of Geriatrics and Palliative Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.|Geriatric Research, Education and Clinical Care Center, VA Ann Arbor Health System, Ann Arbor, MI 48105, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Yung
authors.affiliation: A. Alfred Taubman Medical Research Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Sakowski
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, MI 48109 USA.|A. Alfred Taubman Medical Research Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Eva L
authors.initials: EL
authors.lastname: Feldman
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D035683:MicroRNAs; C000598624:TARDBP protein, human
keywords: Amyotrophic lateral sclerosis; Epigenetics; MicroRNA